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Sample records for stress disorder alterations

  1. Altered blood coagulation in patients with posttraumatic stress disorder.

    PubMed

    von Känel, Roland; Hepp, Urs; Buddeberg, Claus; Keel, Marius; Mica, Ladislav; Aschbacher, Kirstin; Schnyder, Ulrich

    2006-01-01

    Posttraumatic stress disorder (PTSD) has been associated with an increased cardiovascular risk, though the pathophysiologic mechanisms involved are elusive. A hypercoagulable state before occurrence of coronary thrombosis contributes to atherosclerosis development. We investigated whether PTSD would be associated with increased coagulation activity. We measured resting plasma levels of clotting factor VII activity (FVII:C), FVIII:C, FXII:C, fibrinogen, and D-dimer in 14 otherwise healthy patients with PTSD and in 14 age- and gender-matched, trauma-exposed non-PTSD controls. Categorical and dimensional diagnoses of PTSD were made using the Clinician-Administered PTSD Scale (CAPS) interview. We also investigated to what extent the relationship between PTSD and coagulation measures would be confounded by demographics, cardiovascular risk factors, lifestyle variables, time since trauma, and mood. Coagulation factor levels did not significantly differ between patients with a categorical diagnosis of PTSD and controls while controlling for covariates. In all subjects, FVIII:C was predicted by hyperarousal severity (beta = 0.46, p = .014) independent of covariates and by overall PTSD symptom severity (beta = 0.38, p = .045); the latter association was of borderline significance when separately controlling for gender, smoking, exercise, and anxiety (p values <.07). In patients, fibrinogen was predicted by hyperarousal severity (beta = 0.70, p = .005) and by overall PTSD symptom severity (beta = 0.61, p = .020), with mood partially affecting these associations. FVII:C, fibrinogen, and D-dimer showed no independent association with PTSD symptoms. PTSD may elicit hypercoagulability, even at subthreshold levels, offering one psychobiological pathway by which posttraumatic stress might contribute to atherosclerosis progression and clinical cardiovascular disease.

  2. Stress-induced alterations in prefrontal dendritic spines: Implications for post-traumatic stress disorder.

    PubMed

    Moench, Kelly M; Wellman, Cara L

    2015-08-05

    The medial prefrontal cortex (mPFC) is involved in a variety of important functions including emotional regulation, HPA axis regulation, and working memory. It also demonstrates remarkable plasticity in an experience-dependent manner. There is extensive evidence that stressful experiences can produce profound changes in the morphology of neurons within mPFC with a variety of behavioral consequences. The deleterious behavioral outcomes associated with mPFC dysfunction have been implicated in multiple psychopathologies, including post-traumatic stress disorder (PTSD). Given the prevalence of these disorders, a deeper understanding of the cellular mechanisms underlying stress-induced morphological changes in mPFC is critical, and could lead to improved therapeutic treatments. Here we give a brief review of recent studies examining the mechanisms underlying changes in mPFC pyramidal neuron dendritic spines - the primary sites of excitatory input in cortical pyramidal neurons. We begin with an overview of the effects of chronic stress on mPFC dendritic spine density and morphology followed by proposed mechanisms for these changes. We then discuss the time course of stress effects on mPFC as well as potential intercellular influences. Given that many psychopathologies, including PTSD, have different prevalence rates among men and women, we end with a discussion of the sex differences that have been observed in morphological changes in mPFC. Future directions and implications for PTSD are discussed throughout. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Alterations in stress reactivity after long-term treatment with paroxetine in women with posttraumatic stress disorder.

    PubMed

    Vermetten, Eric; Vythilingam, Meena; Schmahl, Christian; DE Kloet, Carien; Southwick, Steven M; Charney, Dennis S; Bremner, J Douglas

    2006-07-01

    Posttraumatic stress disorder (PTSD) is typically accompanied by both acute and chronic alterations in the stress response. These alterations have mostly been described in individuals under baseline conditions, but studies have also used a challenge model to assess the role of the hypothalamic-pituitary-adrenal (HPA) axis in the stress response. The purpose of this article was to assess the effect of long-term treatment with the selective reuptake inhibitor (SSRI), paroxetine, on stress reactivity in patients with PTSD. We assessed diurnal salivary cortisol and urinary cortisol as well as cortisol, heart rate, and behavioral responses to a standardized cognitive stress challenge, in 13 female patients with chronic PTSD before and after 12 months of paroxetine treatment. Treatment resulted in a significant decrease in PTSD symptoms. Twenty-four-hour urinary cortisol was lower compared to base line after successful treatment. Treatment resulted in a decrease of salivary cortisol levels on all time points on a diurnal curve. Despite similar stress perception, cortisol response to the cognitive stress challenge resulted in a 26.5% relative decrease in stress-induced salivary cortisol with treatment. These results suggest that successful treatment with SSRI in chronic PTSD is associated with a trend for a decrease in baseline diurnal cortisol and with reduced cortisol reactivity to stress.

  4. Role of endocrine and inflammatory alterations in comorbid somatic diseases of post-traumatic stress disorder.

    PubMed

    Rohleder, N; Karl, A

    2006-12-01

    Since its first description in the Diagnostic and Statistical Manual for Mental Disorders, post-traumatic stress disorder (PTSD) has been characterized as a disorder of altered affective functioning which causes tremendous distress. In addition, it has been recognized that PTSD is not only accompanied by ''poor health'' but also by a number of specific and non-specific ''somatic'' pathologies, such as cardiovascular, autoimmune and physical complaints/chronic pain. It has been hypothesized that alterations of the hypothalamic-pituitary-adrenal (HPA) axis, the sympathetic-adrenal-medullary (SAM) and the immune system may mediate or facilitate these somatic conditions. The aims of this review are to summarize studies that report altered somatic functioning in PTSD and to review how endocrine and immune function differentially affect PTSD-related somatic malfunction. It is hypothesized that alterations of HPA axis and SAM system permit disinhibition of inflammatory mechanisms, which in turn foster the development of somatic diseases as well as self-reported physical complaints.

  5. Youth Offspring of Mothers with Posttraumatic Stress Disorder Have Altered Stress Reactivity in Response to a Laboratory Stressor

    PubMed Central

    Danielson, Carla Kmett; Hankin, Benjamin L.; Badanes, Lisa S.

    2015-01-01

    Summary Parental Posttraumatic Stress Disorder (PTSD), particularly maternal PTSD, confers risk for stress-related psychopathology among offspring. Altered hypothalamic-pituitary-adrenal (HPA) axis functioning is one mechanism proposed to explain transmission of this intergenerational risk. Investigation of this mechanism has been largely limited to general stress response (e.g., diurnal cortisol), rather than reactivity in response to an acute stressor. We examined cortisol reactivity in response to a laboratory stressor among offspring of mothers with a lifetime diagnosis of PTSD (n=36) and age- and gender- matched control offspring of mothers without PTSD (n=36). Youth (67% girls; mean age = 11.4, SD = 2.6) participated in a developmentally sensitive laboratory stressor and had salivary cortisol assessed five times (one pre-stress, one immediate post-stress, and three recovery measures, spaced 15 minutes apart). Results were consistent with the hypothesis that offspring of mothers with PTSD would exhibit a dysregulated, blunted cortisol reactivity profile and control offspring would display the expected adaptive peak in cortisol response to challenge profile. Findings were maintained after controlling for youth traumatic event history, physical anxiety symptoms, and depression, as well as maternal depression. This finding contributes to the existing literature indicating that attenuated HPA axis functioning, inclusive of hyposecretion of cortisol in response to acute stress, is robust among youth of mothers with PTSD. Future research is warranted in elucidating cortisol reactivity as a link between maternal PTSD and stress-related psychopathology vulnerability among offspring. PMID:25622009

  6. Youth offspring of mothers with posttraumatic stress disorder have altered stress reactivity in response to a laboratory stressor.

    PubMed

    Danielson, Carla Kmett; Hankin, Benjamin L; Badanes, Lisa S

    2015-03-01

    Parental Posttraumatic Stress Disorder (PTSD), particularly maternal PTSD, confers risk for stress-related psychopathology among offspring. Altered hypothalamic-pituitary-adrenal (HPA) axis functioning is one mechanism proposed to explain transmission of this intergenerational risk. Investigation of this mechanism has been largely limited to general stress response (e.g., diurnal cortisol), rather than reactivity in response to an acute stressor. We examined cortisol reactivity in response to a laboratory stressor among offspring of mothers with a lifetime diagnosis of PTSD (n=36) and age- and gender- matched control offspring of mothers without PTSD (n=36). Youth (67% girls; mean age=11.4, SD=2.6) participated in a developmentally sensitive laboratory stressor and had salivary cortisol assessed five times (one pre-stress, one immediate post-stress, and three recovery measures, spaced 15min apart). Results were consistent with the hypothesis that offspring of mothers with PTSD would exhibit a dysregulated, blunted cortisol reactivity profile, and control offspring would display the expected adaptive peak in cortisol response to challenge profile. Findings were maintained after controlling for youth traumatic event history, physical anxiety symptoms, and depression, as well as maternal depression. This finding contributes to the existing literature indicating that attenuated HPA axis functioning, inclusive of hyposecretion of cortisol in response to acute stress, is robust among youth of mothers with PTSD. Future research is warranted in elucidating cortisol reactivity as a link between maternal PTSD and stress-related psychopathology vulnerability among offspring.

  7. Alterations in cognitive flexibility in a rat model of post-traumatic stress disorder.

    PubMed

    George, Sophie A; Rodriguez-Santiago, Mariana; Riley, John; Abelson, James L; Floresco, Stan B; Liberzon, Israel

    2015-06-01

    Exposure to stressful or traumatic events is associated with increased vulnerability to post-traumatic stress disorder (PTSD). This vulnerability may be partly mediated by effects of stress on the prefrontal cortex (PFC) and associated circuitry. The PFC mediates critical cognitive functions, including cognitive flexibility, which reflects an organism's ability to adaptively alter behavior in light of changing contingencies. Prior work suggests that chronic or acute stress exerts complex effects on different forms of cognitive flexibility, via actions on the PFC. Similarly, PFC dysfunction is reported in PTSD, as are executive function deficits. Animal models that permit study of the effects of stress/trauma on cognitive flexibility may be useful in illuminating ways in which stress-linked cognitive changes contribute to PTSD. Here, we examined the behavioral effects of a rodent model of PTSD - single prolonged stress (SPS) - on performance of two forms of cognitive flexibility: reversal learning and strategy set-shifting. SPS did not impair acquisition of either a response or visual-cue discrimination but did cause slight impairments in the retrieval of the visual-cue rule. During response discrimination reversal, SPS rats made more perseverative errors. In comparison, during set-shifting from the visual-cue to response discrimination, SPS rats did not show enhanced perseveration, but did display increased never-reinforced errors, indicative of impairment in selecting a novel strategy. These data demonstrate that SPS leads to a complex and intriguing pattern of deficits in flexible responding and suggest that impairments in executive functioning associated with PTSD could, in part, be a neuro-cognitive consequence of trauma exposure. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. HPA- and HPT-axis alterations in chronic posttraumatic stress disorder.

    PubMed

    Olff, Miranda; Güzelcan, Yener; de Vries, Giel-Jan; Assies, Johanna; Gersons, Berthold P R

    2006-11-01

    Posttraumatic stress disorder (PTSD) has been associated with dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis as well as of the hypothalamus-pituitary-thyroid (HPT) axis. Findings have not been consistent and may depend on methodological issues like controlling for relevant variables. This study examines the levels of six HPA and HPT-axis related hormones in civilian PTSD patients without psychotropic medication. In a cross sectional study, 39 chronic PTSD patients and 44 healthy volunteers were included. Psychometric instruments included SCID, SI-PTSD, IES-R and BDI. The plasma hormones levels assessed were cortisol, dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEA-S), prolactin, thyrotropin (TSH), and free thyroxin (fT4). Results showed that patients had significantly lower plasma cortisol, prolactin and TSH levels compared to the comparison group. The difference between TSH levels in patients and comparison subjects only emerged after controlling for relevant background variables. Furthermore, the severity of PTSD symptoms was negatively related to cortisol levels. Secondary analyses revealed no statistically significant effect of comorbid depression (26% of patients) on any of the hormone levels. Complex feedback mechanisms are likely to result in altered levels of stress related hormones in PTSD, and results depend on controlling for relevant variables. Further research with longitudinal designs is needed to find out whether these lower hormone levels are preexisting risk factors or consequence of trauma and whether these alterations are deleterious or adaptive.

  9. Perfusion deficits and functional connectivity alterations in patients with post-traumatic stress disorder

    NASA Astrophysics Data System (ADS)

    Liu, Yang; Li, Baojuan; Zhang, Xi; Zhang, Linchuan; Li, Liang; Lu, Hongbing

    2016-03-01

    To explore the alteration in cerebral blood flow (CBF) and functional connectivity between survivors with recent onset post-traumatic stress disorder (PTSD) and without PTSD, survived from the same coal mine flood disaster. In this study, a processing pipeline using arterial spin labeling (ASL) sequence was proposed. Considering low spatial resolution of ASL sequence, a linear regression method was firstly used to correct the partial volume (PV) effect for better CBF estimation. Then the alterations of CBF between two groups were analyzed using both uncorrected and PV-corrected CBF maps. Based on altered CBF regions detected from the CBF analysis as seed regions, the functional connectivity abnormities in PTSD patients was investigated. The CBF analysis using PV-corrected maps indicates CBF deficits in the bilateral frontal lobe, right superior frontal gyrus and right corpus callosum of PTSD patients, while only right corpus callosum was identified in uncorrected CBF analysis. Furthermore, the regional CBF of the right superior frontal gyrus exhibits significantly negative correlation with the symptom severity in PTSD patients. The resting-state functional connectivity indicates increased connectivity between left frontal lobe and right parietal lobe. These results indicate that PV-corrected CBF exhibits more subtle perfusion changes and may benefit further perfusion and connectivity analysis. The symptom-specific perfusion deficits and aberrant connectivity in above memory-related regions may be putative biomarkers for recent onset PTSD induced by a single prolonged trauma exposure and help predict the severity of PTSD.

  10. Gray Matter Alterations in Post-Traumatic Stress Disorder, Obsessive-Compulsive Disorder, and Social Anxiety Disorder.

    PubMed

    Cheng, Bochao; Huang, Xiaoqi; Li, Shiguang; Hu, Xinyu; Luo, Ya; Wang, Xiuli; Yang, Xun; Qiu, Changjian; Yang, Yanchun; Zhang, Wei; Bi, Feng; Roberts, Neil; Gong, Qiyong

    2015-01-01

    Post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), and social anxiety disorder (SAD) all bear the core symptom of anxiety and are separately classified in the new DSM-5 system. The aim of the present study is to obtain evidence for neuroanatomical difference for these disorders. We applied voxel-based morphometry (VBM) with Diffeomorphic Anatomical Registration Through Exponentiated Lie to compare gray matter volume (GMV) in magnetic resonance images obtained for 30 patients with PTSD, 29 patients with OCD, 20 patients with SAD, and 30 healthy controls. GMV across all four groups differed in left hypothalamus and left inferior parietal lobule and post hoc analyses revealed that this difference is primarily due to reduced GMV in the PTSD group relative to the other groups. Further analysis revealed that the PTSD group also showed reduced GMV in frontal lobe, temporal lobe, and cerebellum compared to the OCD group, and reduced GMV in frontal lobes bilaterally compared to SAD group. A significant negative correlation with anxiety symptoms is observed for GMV in left hypothalamus in three disorder groups. We have thus found evidence for brain structure differences that in future could provide biomarkers to potentially support classification of these disorders using MRI.

  11. Gray Matter Alterations in Post-Traumatic Stress Disorder, Obsessive–Compulsive Disorder, and Social Anxiety Disorder

    PubMed Central

    Cheng, Bochao; Huang, Xiaoqi; Li, Shiguang; Hu, Xinyu; Luo, Ya; Wang, Xiuli; Yang, Xun; Qiu, Changjian; Yang, Yanchun; Zhang, Wei; Bi, Feng; Roberts, Neil; Gong, Qiyong

    2015-01-01

    Post-traumatic stress disorder (PTSD), obsessive–compulsive disorder (OCD), and social anxiety disorder (SAD) all bear the core symptom of anxiety and are separately classified in the new DSM-5 system. The aim of the present study is to obtain evidence for neuroanatomical difference for these disorders. We applied voxel-based morphometry (VBM) with Diffeomorphic Anatomical Registration Through Exponentiated Lie to compare gray matter volume (GMV) in magnetic resonance images obtained for 30 patients with PTSD, 29 patients with OCD, 20 patients with SAD, and 30 healthy controls. GMV across all four groups differed in left hypothalamus and left inferior parietal lobule and post hoc analyses revealed that this difference is primarily due to reduced GMV in the PTSD group relative to the other groups. Further analysis revealed that the PTSD group also showed reduced GMV in frontal lobe, temporal lobe, and cerebellum compared to the OCD group, and reduced GMV in frontal lobes bilaterally compared to SAD group. A significant negative correlation with anxiety symptoms is observed for GMV in left hypothalamus in three disorder groups. We have thus found evidence for brain structure differences that in future could provide biomarkers to potentially support classification of these disorders using MRI. PMID:26347628

  12. Epigenetic alterations of the BDNF gene in combat-related post-traumatic stress disorder.

    PubMed

    Kim, T Y; Kim, S J; Chung, H G; Choi, J H; Kim, S H; Kang, J I

    2017-02-01

    Brain-derived neurotrophic factor (BDNF) plays a crucial role in modulating resilience and vulnerability to stress. The aim of this study was to investigate whether epigenetic regulation of the BDNF gene is a biomarker of post-traumatic stress disorder (PTSD) development among veterans exposed to combat in the Vietnam War. Using the Clinician-Administered PTSD Scale, combat veterans were grouped into those with (n = 126) and without (n = 122) PTSD. DNA methylation levels at four CpG sites within the BDNF promoter I region were quantified in the peripheral blood using pyrosequencing. The effects of BDNF DNA methylation levels and clinical variables on the diagnosis of PTSD were tested using binary logistic regression analysis. Subjects with PTSD showed a higher DNA methylation of four CpG sites at the BDNF promoter compared with those without PTSD. High methylation levels at the BDNF promoter CpG site, high combat exposure, and alcohol problems were significantly associated with PTSD diagnosis. This study demonstrated an association between higher DNA methylation of the BDNF promoter and PTSD diagnosis in combat-exposed individuals. Our findings suggest that altered BDNF methylation may be a valuable biomarker of PTSD after trauma exposure. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Patients with posttraumatic stress disorder exhibit an altered phenotype of regulatory T cells

    PubMed Central

    2014-01-01

    Background Regulatory T cells (Tregs) play a key role in immune homeostasis in vivo. Tregs have a critical role in preventing the development of autoimmune diseases and defects in Treg function are implicated in various autoimmune disorders. Individuals with posttraumatic stress disorder (PTSD) have higher prevalence of autoimmune disorders than the general population. We hypothesized that war veterans with PTSD would exhibit a decreased number and/or altered phenotype of Tregs. Methods We analyzed peripheral blood mononuclear cells (PBMCs) of patients with PTSD (N = 21) (mean age = 45.9) and age-matched healthy controls (N = 23) (mean age = 45.7) to determine the proportion of Tregs and their phenotype according to the expression of CD127 and HLA-DR markers which describe the differentiation stages of Tregs. In addition, we analyzed the expression of membrane ectoenzyme CD39 on Tregs of the study groups, an important component of the suppressive machinery of Tregs. Results We found no differences in the proportion of Tregs between PTSD patients and controls, but PTSD patients had a higher percentage of CD127-HLA-DR- Tregs and a lower percentage of CD127loHLA-DR+ Tregs compared to controls. There was no difference in expression of CD39 on Tregs of the study groups. Conclusions Although the proportions of Tregs in PTSD patients were unchanged, we found that they exhibit a different phenotype of Tregs that might be less suppressive. Impaired differentiation and function of Tregs is likely involved in disruption of immune homeostasis in PTSD. PMID:25670936

  14. Alterations in empathic responding among women with posttraumatic stress disorder associated with childhood trauma.

    PubMed

    Parlar, Melissa; Frewen, Paul; Nazarov, Anthony; Oremus, Carolina; MacQueen, Glenda; Lanius, Ruth; McKinnon, Margaret C

    2014-05-01

    Although studies increasingly point toward problems with social cognition among individuals with posttraumatic stress disorder (PTSD), few studies have assessed empathic responding. The aim of the current study was to investigate empathic responding in women with PTSD related to childhood trauma, and the contribution of parental bonding to empathic abilities in this sample. Participants with PTSD (n = 29) and sex- and age-matched healthy controls (n = 20) completed two self-report empathy measures, the Interpersonal Reactivity Index (IRI) and the Toronto Empathy Questionnaire (TEQ), and a self-report measure of attachment, the Parental Bonding Instrument (PBI). Women with PTSD, relative to controls, reported significantly lower levels of empathic concern (r = 0.29) and perspective taking (r = 0.30), yet significantly higher levels of personal distress (r = 0.45) on the IRI. Women with PTSD also reported elevated scores on the TEQ (η (2) = 0.13). Levels of paternal care on the PBI, rather than childhood trauma severity or PTSD symptom severity best predicted perspective taking scores on the IRI in the PTSD sample (R (2) = 0.20). Women with PTSD associated with childhood trauma reported alterations among different domains of empathic functioning that may be related to low levels of paternal care.

  15. Altered resting-state functional activity in posttraumatic stress disorder: A quantitative meta-analysis

    PubMed Central

    Wang, Ting; Liu, Jia; Zhang, Junran; Zhan, Wang; Li, Lei; Wu, Min; Huang, Hua; Zhu, Hongyan; Kemp, Graham J.; Gong, Qiyong

    2016-01-01

    Many functional neuroimaging studies have reported differential patterns of spontaneous brain activity in posttraumatic stress disorder (PTSD), but the findings are inconsistent and have not so far been quantitatively reviewed. The present study set out to determine consistent, specific regional brain activity alterations in PTSD, using the Effect Size Signed Differential Mapping technique to conduct a quantitative meta-analysis of resting-state functional neuroimaging studies of PTSD that used either a non-trauma (NTC) or a trauma-exposed (TEC) comparison control group. Fifteen functional neuroimaging studies were included, comparing 286 PTSDs, 203 TECs and 155 NTCs. Compared with NTC, PTSD patients showed hyperactivity in the right anterior insula and bilateral cerebellum, and hypoactivity in the dorsal medial prefrontal cortex (mPFC); compared with TEC, PTSD showed hyperactivity in the ventral mPFC. The pooled meta-analysis showed hypoactivity in the posterior insula, superior temporal, and Heschl’s gyrus in PTSD. Additionally, subgroup meta-analysis (non-medicated subjects vs. NTC) identified abnormal activation in the prefrontal-limbic system. In meta-regression analyses, mean illness duration was positively associated with activity in the right cerebellum (PTSD vs. NTC), and illness severity was negatively associated with activity in the right lingual gyrus (PTSD vs. TEC). PMID:27251865

  16. Alterations in empathic responding among women with posttraumatic stress disorder associated with childhood trauma

    PubMed Central

    Parlar, Melissa; Frewen, Paul; Nazarov, Anthony; Oremus, Carolina; MacQueen, Glenda; Lanius, Ruth; McKinnon, Margaret C

    2014-01-01

    Objective Although studies increasingly point toward problems with social cognition among individuals with posttraumatic stress disorder (PTSD), few studies have assessed empathic responding. The aim of the current study was to investigate empathic responding in women with PTSD related to childhood trauma, and the contribution of parental bonding to empathic abilities in this sample. Methods Participants with PTSD (n = 29) and sex- and age-matched healthy controls (n = 20) completed two self-report empathy measures, the Interpersonal Reactivity Index (IRI) and the Toronto Empathy Questionnaire (TEQ), and a self-report measure of attachment, the Parental Bonding Instrument (PBI). Results Women with PTSD, relative to controls, reported significantly lower levels of empathic concern (r = 0.29) and perspective taking (r = 0.30), yet significantly higher levels of personal distress (r = 0.45) on the IRI. Women with PTSD also reported elevated scores on the TEQ (η2 = 0.13). Levels of paternal care on the PBI, rather than childhood trauma severity or PTSD symptom severity best predicted perspective taking scores on the IRI in the PTSD sample (R2 = 0.20). Conclusion Women with PTSD associated with childhood trauma reported alterations among different domains of empathic functioning that may be related to low levels of paternal care. PMID:24944867

  17. Altered Pain Perception and Fear-Learning Deficits in Subjects With Posttraumatic Stress Disorder.

    PubMed

    Jenewein, Josef; Erni, Jeannine; Moergeli, Hanspeter; Grillon, Christian; Schumacher, Sonja; Mueller-Pfeiffer, Christoph; Hassanpour, Katayun; Seiler, Annina; Wittmann, Lutz; Schnyder, Ulrich; Hasler, Gregor

    2016-12-01

    There is growing evidence that fear-learning abnormalities are involved in the development of posttraumatic stress disorder (PTSD) and chronic pain. More than 50% of PTSD patients suffer from chronic pain. This study aimed to examine the role of fear-learning deficits in the link between pain perception and PTSD. We included 19 subjects with PTSD and 21 age- and sex-matched healthy control subjects in a fear-conditioning experiment. The conditioned stimulus (CS) consisted of visual signs flashed upon a screen in front of each subject. The unconditioned stimulus was either a low or high temperature impulse delivered through a thermal contact thermode on the subjects' hand. A designation of 'CS-' was assigned to CS always followed by nonpainful low-temperature stimuli; a designation of 'CS+' was given to CS that were randomly followed by either a low or a more painful high temperature. Skin conductance was used as a physiological marker of fear. In healthy control subjects, CS+ induced more fear than CS-, and a low-temperature stimulus induced less subjective pain after CS- than after CS+. PTSD subjects failed to demonstrate such adaptive conditioning. Fear ratings after CS presentation were significantly higher in the PTSD group than in the control group. There were significant interaction effects between group and the type of CS on fear and pain ratings. Fear-learning deficits are a potentially promising, specific psychopathological factor in altered pain perception associated with PTSD. Deficits in safety learning may increase fear and, consequently, pain sensations. These findings may contribute to elucidating the pathogenesis behind the highly prevalent comorbidity that exists between PTSD and pain disorders, and to developing new treatments. This study provides new insights into the pathogenesis of chronic pain in patients with PTSD. The findings may help to develop new treatment strategies for this highly prevalent comorbidity in PTSD. Copyright © 2016

  18. Prenatal Stress Alters Progestogens to Mediate Susceptibility to Sex-Typical, Stress-Sensitive Disorders, such as Drug Abuse: A Review

    PubMed Central

    Frye, Cheryl A.; Paris, Jason J.; Osborne, Danielle M.; Campbell, Joannalee C.; Kippin, Tod E.

    2011-01-01

    Maternal–offspring interactions begin prior to birth. Experiences of the mother during gestation play a powerful role in determining the developmental programming of the central nervous system. In particular, stress during gestation alters developmental programming of the offspring resulting in susceptibility to sex-typical and stress-sensitive neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. However, neither these effects, nor the underlying mechanisms, are well understood. Our hypothesis is that allopregnanolone, during gestation, plays a particularly vital role in mitigating effects of stress on the developing fetus and may mediate, in part, alterations apparent throughout the lifespan. Specifically, altered balance between glucocorticoids and progestogens during critical periods of development (stemming from psychological, immunological, and/or endocrinological stressors during gestation) may permanently influence behavior, brain morphology, and/or neuroendocrine-sensitive processes. 5α-reduced progestogens are integral in the developmental programming of sex-typical, stress-sensitive, and/or disorder-relevant phenotypes. Prenatal stress (PNS) may alter these responses and dysregulate allopregnanolone and its normative effects on stress axis function. As an example of a neurodevelopmental, neuropsychiatric, and/or neurodegenerative process, this review focuses on responsiveness to drugs of abuse, which is sensitive to PNS and progestogen milieu. This review explores the notion that allopregnanolone may effect, or be influenced by, PNS, with consequences for neurodevelopmental-, neuropsychiatric-, and/or neurodegenerative- relevant processes, such as addiction. PMID:22022315

  19. Prenatal Stress Alters Progestogens to Mediate Susceptibility to Sex-Typical, Stress-Sensitive Disorders, such as Drug Abuse: A Review.

    PubMed

    Frye, Cheryl A; Paris, Jason J; Osborne, Danielle M; Campbell, Joannalee C; Kippin, Tod E

    2011-01-01

    Maternal-offspring interactions begin prior to birth. Experiences of the mother during gestation play a powerful role in determining the developmental programming of the central nervous system. In particular, stress during gestation alters developmental programming of the offspring resulting in susceptibility to sex-typical and stress-sensitive neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. However, neither these effects, nor the underlying mechanisms, are well understood. Our hypothesis is that allopregnanolone, during gestation, plays a particularly vital role in mitigating effects of stress on the developing fetus and may mediate, in part, alterations apparent throughout the lifespan. Specifically, altered balance between glucocorticoids and progestogens during critical periods of development (stemming from psychological, immunological, and/or endocrinological stressors during gestation) may permanently influence behavior, brain morphology, and/or neuroendocrine-sensitive processes. 5α-reduced progestogens are integral in the developmental programming of sex-typical, stress-sensitive, and/or disorder-relevant phenotypes. Prenatal stress (PNS) may alter these responses and dysregulate allopregnanolone and its normative effects on stress axis function. As an example of a neurodevelopmental, neuropsychiatric, and/or neurodegenerative process, this review focuses on responsiveness to drugs of abuse, which is sensitive to PNS and progestogen milieu. This review explores the notion that allopregnanolone may effect, or be influenced by, PNS, with consequences for neurodevelopmental-, neuropsychiatric-, and/or neurodegenerative- relevant processes, such as addiction.

  20. The influence of stress on neuroinflammation and alterations in brain structure and function in major depressive disorder.

    PubMed

    Kim, Yong-Ku; Won, Eunsoo

    2017-06-30

    Major depressive disorder (MDD) is a condition which has often been associated with chronic stress. The sympathetic nervous system is continuously activated without the normal counteraction of the parasympathetic nervous system under the influence of chronic stress. As a result, epinephrine and norepinephrine levels are increased, and acetylcholine levels are decreased, which in turn can increase the levels of pro-inflammatory cytokines. Peripheral inflammatory responses can access the brain, with neuroinflammation contributing to the increase in neurotoxic kynurenine pathway metabolites such as 3-hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid, and decrease in neuroprotective metabolites such as kynurenic acid. Pro-inflammatory cytokines can also exert direct neurotoxic effects on specific brain regions. Previous imaging studies have reported associations between pro-inflammatory states and alterations in brain regions involved in emotional regulation, including the hippocampus, amygdala and anterior cingulate cortex. Alterations in structure and function of such brain areas due to the neurotoxic effects of increased inflammation may be associated with the pathophysiology of depression. This review focuses the influence of stress on neuroinflammation which may cause alterations in brain structure and function in MDD. Copyright © 2017. Published by Elsevier B.V.

  1. Nitric oxide synthase and nitric oxide alterations in chronically stressed rats: a model for nitric oxide in major depressive disorder.

    PubMed

    Gao, Shang-Feng; Lu, Yun-Rong; Shi, Li-Gen; Wu, Xue-Yan; Sun, Bo; Fu, Xin-Yan; Luo, Jian-Hong; Bao, Ai-Min

    2014-09-01

    Nitric oxide (NO) and NO synthase-1 (NOS1) are involved in the stress response and in depression. We compared NOS-NO alterations in rats exposed to chronic unpredictable stress (CUS) with alterations in major depressive disorder (MDD) in humans. In the hypothalamus of male CUS rats we determined NOS activity, and in the paraventricular nucleus (PVN) we determined NOS1-immunoreactive (ir) cell densities and co-localization of NOS1 with stress-related neuropeptides corticotropin-releasing hormone (CRH), vasopressin (AVP) or oxytocin (OXT). We measured plasma NO levels and cortisol in male medicine-naïve MDD patients and plasma NO and corticosterone (CORT) in CUS rats. In the CUS rat total NOS activity in the hypothalamus (P=0.018) and NOS1-ir cell density in the PVN were both significantly decreased (P=0.018), while NOS1 staining was mainly expressed in OXT-ir neurons in this nucleus. Interestingly, plasma NO levels were significantly increased both in male CUS rats (P=0.001) and in male MDD patients (P<0.001). Plasma CORT levels were increased in male CUS rats (P=0.001), while male MDD patients did not show a significant change in cortisol levels. In conclusion, the changes in plasma and hypothalamic NOS-NO of CUS rats and MDD were similar. The male CUS rat model may thus help us with our investigation of the mechanism underlying NOS-NO alterations in depression.

  2. Altered Microstructural Caudate Integrity in Posttraumatic Stress Disorder but Not Traumatic Brain Injury

    PubMed Central

    Waltzman, Dana; Soman, Salil; Fairchild, J. Kaci; Kinoshita, Lisa M.; Wintermark, Max; Ashford, J. Wesson; Yesavage, Jerome; Williams, Leanne

    2017-01-01

    Objective Given the high prevalence and comorbidity of combat-related PTSD and TBI in Veterans, it is often difficult to disentangle the contributions of each disorder. Examining these pathologies separately may help to understand the neurobiological basis of memory impairment in PTSD and TBI independently of each other. Thus, we investigated whether a) PTSD and TBI are characterized by subcortical structural abnormalities by examining diffusion tensor imaging (DTI) metrics and volume and b) if these abnormalities were specific to PTSD versus TBI. Method We investigated whether individuals with PTSD or TBI display subcortical structural abnormalities in memory regions by examining DTI metrics and volume of the hippocampus and caudate in three groups of Veterans: Veterans with PTSD, Veterans with TBI, and Veterans with neither PTSD nor TBI (Veteran controls). Results While our results demonstrated no macrostructural differences among the groups in these regions, there were significant alterations in microstructural DTI indices in the caudate for the PTSD group but not the TBI group compared to Veteran controls. Conclusions The result of increased mean, radial, and axial diffusivity, and decreased fractional anisotropy in the caudate in absence of significant volume atrophy in the PTSD group suggests the presence of subtle abnormalities evident only at a microstructural level. The caudate is thought to play a role in the physiopathology of PTSD, and the habit-like behavioral features of the disorder could be due to striatal-dependent habit learning mechanisms. Thus, DTI appears to be a vital tool to investigate subcortical pathology, greatly enhancing the ability to detect subtle brain changes in complex disorders. PMID:28114393

  3. Posttraumatic Stress Disorder

    MedlinePlus

    ... ON THIS TOPIC Helping Kids Cope With Stress Obsessive-Compulsive Disorder Posttraumatic Stress Disorder Special Needs Factsheet Taking Your ... Childhood Stress About Teen Suicide Sadness and Depression Obsessive-Compulsive Disorder Phobias Five Steps for Fighting Stress Going to ...

  4. Metabolic Stress and Disorders Related to Alterations in Mitochondrial Fission or Fusion

    PubMed Central

    Babbar, Mansi; Sheikh, M. Saeed

    2014-01-01

    Mitochondrial morphology and metabolism play an important role in cellular homeostasis. Recent studies have shown that the fidelity of mitochondrial morphology is important in maintaining mitochondrial shape, number, size, membrane potential, ATP synthesis, mtDNA, motility, signaling, quality control, response to cellular stress, mitophagy and apoptosis. This article provides an overview of the current state of knowledge of the fission and fusion machinery with a focus on the mechanisms underlying the regulation of the mitochondrial morphology and cellular energy state. Several lines of evidence indicate that dysregulation of mitochondrial fission or fusion is associated with mitochondrial dysfunction, which in turn impacts mitophagy and apoptosis. Metabolic disorders are also associated with dysregulation of fission or fusion and the available lines of evidence point to a bidirectional interplay between the mitochondrial fission or fusion reactions and bioenergetics. Clearly, more in-depth studies are needed to fully elucidate the mechanisms that control mitochondrial fission and fusion. It is envisioned that the outcome of such studies will improve the understanding of the molecular basis of related metabolic disorders and also facilitate the development of better therapeutics. PMID:24533171

  5. Neural correlates of altered pain response in women with posttraumatic stress disorder from intimate partner violence.

    PubMed

    Strigo, Irina A; Simmons, Alan N; Matthews, Scott C; Grimes, Erin M; Allard, Carolyn B; Reinhardt, Lindsay E; Paulus, Martin P; Stein, Murray B

    2010-09-01

    Intimate partner violence (IPV) is one of the most common causes of posttraumatic stress disorder (PTSD) in women. Women with IPV-related PTSD often experience comorbid chronic pain and pain-related disability. Despite the high comorbidity between PTSD and chronic pain, recent evidence suggests that male veterans with combat-related PTSD report decreased sensitivity to experimental pain. The aim of this study was to examine the neurobehavioral correlates of experimental pain in women with IPV-related PTSD. Functional magnetic resonance neuroimaging data were collected during an event-related experimental pain paradigm that was administered twice to 23 women with IPV-related PTSD and 15 age-, race- and education-comparable nontraumatized control women. Brief thermal heat stimuli were repeatedly applied to the left volar forearm, and subjects rated the perceived temperature intensity with a button-box. Women with IPV-related PTSD relative to nontraumatized control women showed: 1) increased activation of right middle insula and right dorsolateral prefrontal cortex during initial painful stimulation, and 2) subsequent decrease in subjective intensity ratings with repeated exposure to pain, which was accompanied by attenuation of activation within right anterior insula that was associated with avoidance symptoms of PTSD. These results suggest that women with IPV-related PTSD show dysregulated functional brain activity during pain processing, which might drive maladaptive coping mechanisms, such as avoidance and numbing. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  6. Morphologic alterations in the corpus callosum in abuse-related posttraumatic stress disorder: a preliminary study.

    PubMed

    Kitayama, Noriyuki; Brummer, Marijn; Hertz, Lois; Quinn, Sinead; Kim, Yoshiharu; Bremner, J Douglas

    2007-12-01

    Magnetic resonance imaging (MRI) studies in children with maltreatment-related posttraumatic stress disorder (PTSD) have demonstrated smaller corpus callosum area, with the greatest magnitude of change in posterior portions of the corpus callosum. The purpose of this study was to measure corpus callosum area in adult female patients with childhood abuse-related PTSD and comparison subjects. MRI was used to measure the midsagittal area of the corpus callosum as well as subregions of the corpus callosum in 9 female subjects with abuse-related PTSD and 9 healthy female subjects. No differences were found in total area of the corpus callosum or in individual subregions, but the subregion/total area ratio was significantly smaller in posterior midbody in PTSD compared with the healthy subjects. These results suggest that relatively smaller areas of the posterior midbody of the corpus callosum are associated with childhood abuse related PTSD in adults; these findings are consistent with findings in children with abuse-related PTSD.

  7. Alterations in HPA-axis and autonomic nervous system functioning in childhood anxiety disorders point to a chronic stress hypothesis.

    PubMed

    Dieleman, Gwendolyn C; Huizink, Anja C; Tulen, Joke H M; Utens, Elisabeth M W J; Creemers, Hanneke E; van der Ende, Jan; Verhulst, Frank C

    2015-01-01

    It is of debate whether or not childhood anxiety disorders (AD) can be captured by one taxonomic construct. This study examined whether perceived arousal (PA), autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis measures can distinguish children with different primary diagnoses of clinical anxiety disorders (AD) from each other, and from a general population reference group (GP). The study sample consisted of 152 AD children (comparing separation anxiety disorder, generalized anxiety disorder, social phobia and specific phobia), aged 8- to 12-years, and 200 same-aged reference children. HPA-axis functioning was measured by a diurnal cortisol profile. ANS functioning was measured by continuous measures of skin conductance level in rest and during a mental arithmetic task and high frequency heart rate variability in rest. PA was assessed by a questionnaire. The AD sample showed lower high frequency heart rate variability during rest, heightened anticipatory PA, higher basal and reactive skin conductance levels and lower basal HPA-axis functioning compared to the GP sample. The existence of three or more clinical disorders, i.e. a high clinical 'load', was associated with lower basal HPA-axis functioning, higher skin conductance level and lower posttest PA. Specific phobia could be discerned from social phobia and separation anxiety disorder on higher skin conductance level. Our findings indicated that children with AD have specific psychophysiological characteristics, which resemble the psychophysiological characteristics of chronic stress. A high clinical 'load' is associated with an altered ANS and HPA-axis functioning. Overall, ANS and HPA-axis functioning relate to AD in general, accept for specific phobia. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Altered resting-state functional connectivity in post-traumatic stress disorder: a perfusion MRI study

    NASA Astrophysics Data System (ADS)

    Li, Baojuan; Liu, Jian; Liu, Yang; Lu, Hong-Bing; Yin, Hong

    2013-03-01

    The majority of studies on posttraumatic stress disorder (PTSD) so far have focused on delineating patterns of activations during cognitive processes. Recently, more and more researches have started to investigate functional connectivity in PTSD subjects using BOLD-fMRI. Functional connectivity analysis has been demonstrated as a powerful approach to identify biomarkers of different brain diseases. This study aimed to detect resting-state functional connectivity abnormities in patients with PTSD using arterial spin labeling (ASL) fMRI. As a completely non-invasive technique, ASL allows quantitative estimates of cerebral blood flow (CBF). Compared with BOLD-fMRI, ASL fMRI has many advantages, including less low-frequency signal drifts, superior functional localization, etc. In the current study, ASL images were collected from 10 survivors in mining disaster with recent onset PTSD and 10 survivors without PTSD. Decreased regional CBF in the right middle temporal gyrus, lingual gyrus, and postcentral gyrus was detected in the PTSD patients. Seed-based resting-state functional connectivity analysis was performed using an area in the right middle temporal gyrus as region of interest. Compared with the non-PTSD group, the PTSD subjects demonstrated increased functional connectivity between the right middle temporal gyrus and the right superior temporal gyrus, the left middle temporal gyrus. Meanwhile, decreased functional connectivity between the right middle temporal gyrus and the right postcentral gyrus, the right superior parietal lobule was also found in the PTSD patients. This is the first study which investigated resting-state functional connectivity in PTSD using ASL images. The results may provide new insight into the neural substrates of PTSD.

  9. Altered blood oxygen level-dependent signal variability in chronic post-traumatic stress disorder during symptom provocation

    PubMed Central

    Ke, Jun; Zhang, Li; Qi, Rongfeng; Xu, Qiang; Li, Weihui; Hou, Cailan; Zhong, Yuan; Zhang, Zhiqiang; He, Zhong; Li, Lingjiang; Lu, Guangming

    2015-01-01

    Background Recent research suggests that variability in brain signal provides important information about brain function in health and disease. However, it is unknown whether blood oxygen level-dependent (BOLD) signal variability is altered in post-traumatic stress disorder (PTSD). We aimed to identify the BOLD signal variability changes of PTSD patients during symptom provocation and compare the brain patterns of BOLD signal variability with those of brain activation. Methods Twelve PTSD patients and 14 age-matched controls, who all experienced a mining accident, underwent clinical assessment as well as fMRI scanning while viewing trauma-related and neutral pictures. BOLD signal variability and brain activation were respectively examined with standard deviation (SD) and general linear model analysis, and compared between the PTSD and control groups. Multiple regression analyses were conducted to explore the association between PTSD symptom severity and these two brain measures across all subjects as well as in the PTSD group. Results PTSD patients showed increased activation in the middle occipital gyrus compared with controls, and an inverse correlation was found between PTSD symptom severity and brain activation in the hippocampus and anterior cingulate cortex/medial prefrontal cortex. Brain variability analysis revealed increased SD in the insula, anterior cingulate cortex/medial prefrontal cortex, and vermis, and decreased SD in the parahippocapal gyrus, dorsolateral prefrontal cortex, somatosensory cortex, and striatum. Importantly, SD alterations in several regions were found in both traumatic and neutral conditions and were stratified by PTSD symptom severity. Conclusion BOLD signal variability may be a reliable and sensitive biomarker of PTSD, and combining brain activation and brain variability analysis may provide complementary insight into the neural basis of this disorder. PMID:26229476

  10. Altered Olfactory Processing of Stress-Related Body Odors and Artificial Odors in Patients with Panic Disorder

    PubMed Central

    Wintermann, Gloria-Beatrice; Donix, Markus; Joraschky, Peter; Gerber, Johannes; Petrowski, Katja

    2013-01-01

    Background Patients with Panic Disorder (PD) direct their attention towards potential threat, followed by panic attacks, and increased sweat production. Onés own anxiety sweat odor influences the attentional focus, and discrimination of threat or non-threat. Since olfactory projection areas overlap with neuronal areas of a panic-specific fear network, the present study investigated the neuronal processing of odors in general and of stress-related sweat odors in particular in patients with PD. Methods A sample of 13 patients with PD with/ without agoraphobia and 13 age- and gender-matched healthy controls underwent an fMRI investigation during olfactory stimulation with their stress-related sweat odors (TSST, ergometry) as well as artificial odors (peach, artificial sweat) as non-fearful non-body odors. Principal Findings The two groups did not differ with respect to their olfactory identification ability. Independent of the kind of odor, the patients with PD showed activations in fronto-cortical areas in contrast to the healthy controls who showed activations in olfaction-related areas such as the amygdalae and the hippocampus. For artificial odors, the patients with PD showed a decreased neuronal activation of the thalamus, the posterior cingulate cortex and the anterior cingulate cortex. Under the presentation of sweat odor caused by ergometric exercise, the patients with PD showed an increased activation in the superior temporal gyrus, the supramarginal gyrus, and the cingulate cortex which was positively correlated with the severity of the psychopathology. For the sweat odor from the anxiety condition, the patients with PD showed an increased activation in the gyrus frontalis inferior, which was positively correlated with the severity of the psychopathology. Conclusions The results suggest altered neuronal processing of olfactory stimuli in PD. Both artificial odors and stress-related body odors activate specific parts of a fear-network which is associated

  11. Altered default mode network configuration in posttraumatic stress disorder after earthquake: A resting-stage functional magnetic resonance imaging study.

    PubMed

    Zhang, Xiao-Dong; Yin, Yan; Hu, Xiao-Lei; Duan, Lian; Qi, Rongfeng; Xu, Qiang; Lu, Guang-Ming; Li, Ling-Jiang

    2017-09-01

    The neural substrates of posttraumatic stress disorder (PTSD) are still not fully elucidated. Hence, this study is to explore topological alterations of the default mode network (DMN) in victims with PTSD after a magnitude of 8.0 earthquake using resting-state functional magnetic resonance imaging (rs-fMRI).This study was approved by the local ethical review board, and all participants signed written informed consent. Sixty-two PTSD victims from the 2008 Sichuan earthquake and 62 matched exposed controls underwent rs-fMRI. PTSD was diagnosed by Clinician-Administered PTSD Scale, and underwent PTSD Checklist-Civilian Version for symptom scoring. The DMN was analyzed by using graph theoretical approaches. Further, Pearson correlation analysis was performed to correlate neuroimaging metrics to neuropsychological scores in victims with PTSD.Victims with PTSD showed decreased DMN functional connectivity strength between the right superior frontal gyrus and left inferior parietal lobule (IPL), and showed increased functional connectivity between the right IPL and precuneus or left posterior cingulate cortex. It was also found that victims with PTSD exhibited decreased nodal efficiency in right superior frontal gyrus and precuneus, and increased nodal efficiency in right hippocampus/parahippocampus. Apart from that, PTSD showed higher nodal degree in bilateral hippocampus/parahippocampus. In addition, the functional connectivity strength between the right IPL and precuneus correlated negatively to the avoid scores (r = -0.26, P = .04).This study implicates alteration of topological features on the DMN in PTSD victims after major earthquake, and provides new insights into DMN malfunction in PTSD based on graph theory.

  12. Altered lipid peroxidation markers are related to post-traumatic stress disorder (PTSD) and not trauma itself in earthquake survivors.

    PubMed

    Atli, Abdullah; Bulut, Mahmut; Bez, Yasin; Kaplan, İbrahim; Özdemir, Pınar Güzel; Uysal, Cem; Selçuk, Hilal; Sir, Aytekin

    2016-06-01

    The traumatic life events, including earthquakes, war, and interpersonal conflicts, cause a cascade of psychological and biological changes known as post-traumatic stress disorder (PTSD). Malondialdehyde (MDA) is a reliable marker of lipid peroxidation, and paraoxonase is a known antioxidant enzyme. The aims of this study were to investigate the relationship between earthquake trauma, PTSD effects on oxidative stress and the levels of serum paraoxonase 1 (PON1) enzyme activity, and levels of serum MDA. The study was carried out on three groups called: the PTSD group, the traumatized with earthquake exercise group, and healthy control group, which contained 32, 31, and 38 individuals, respectively. Serum MDA levels and PON1 enzyme activities from all participants were measured, and the results were compared across all groups. There were no significant differences between the PTSD patients and non-PTSD earthquake survivors in terms of the study variables. The mean PON1 enzyme activity from PTSD patients was significantly lower, while the mean MDA level was significantly higher than that of the healthy control group (p < 0.01 for both measurements). Similarly, earthquake survivors who did not develop PTSD showed higher MDA levels and lower PON1 activity when compared to healthy controls. However, the differences between these groups did not reach a statistically significant level. Increased MDA level and decreased PON1 activity measured in PTSD patients after earthquake and may suggest increased oxidative stress in these patients. The nonsignificant trends that are observed in lipid peroxidation markers of earthquake survivors may indicate higher impact of PTSD development on these markers than trauma itself. For example, PTSD diagnosis seems to add to the effect of trauma on serum MDA levels and PON1 enzyme activity. Thus, serum MDA levels and PON1 enzyme activity may serve as biochemical markers of PTSD diagnosis.

  13. Improvement of mood and sleep alterations in posttraumatic stress disorder patients by eye movement desensitization and reprocessing.

    PubMed

    Raboni, Mara R; Alonso, Fabiana F D; Tufik, Sergio; Suchecki, Deborah

    2014-01-01

    Posttraumatic stress disorder (PTSD) patients exhibit depressive and anxiety symptoms, in addition to nightmares, which interfere with sleep continuity. Pharmacologic treatment of these sleep problems improves PTSD symptoms, but very few studies have used psychotherapeutic interventions to treat PTSD and examined their effects on sleep quality. Therefore, in the present study, we sought to investigate the effects of Eye Movement Desensitization Reprocessing therapy on indices of mood, anxiety, subjective, and objective sleep. The sample was composed of 11 healthy controls and 13 PTSD patients that were victims of assault and/or kidnapping. All participants were assessed before, and 1 day after, the end of treatment for depressive and anxiety profile, general well-being and subjective sleep by filling out specific questionnaires. In addition, objective sleep patterns were evaluated by polysomnographic recording. Healthy volunteers were submitted to the therapy for three weekly sessions, whereas PTSD patients underwent five sessions, on average. Before treatment, PTSD patients exhibited high levels of anxiety and depression, poor quality of life and poor sleep, assessed both subjectively and objectively; the latter was reflected by increased time of waking after sleep onset. After completion of treatment, patients exhibited improvement in depression and anxiety symptoms, and in quality of life; with indices that were no longer different from control volunteers. Moreover, these patients showed more consolidated sleep, with reduction of time spent awake after sleep onset. In conclusion, Eye Movement Desensitization and Reprocessing was an effective treatment of PTSD patients and improved the associated sleep and psychological symptoms.

  14. Improvement of mood and sleep alterations in posttraumatic stress disorder patients by eye movement desensitization and reprocessing

    PubMed Central

    Raboni, Mara R.; Alonso, Fabiana F. D.; Tufik, Sergio; Suchecki, Deborah

    2014-01-01

    Posttraumatic stress disorder (PTSD) patients exhibit depressive and anxiety symptoms, in addition to nightmares, which interfere with sleep continuity. Pharmacologic treatment of these sleep problems improves PTSD symptoms, but very few studies have used psychotherapeutic interventions to treat PTSD and examined their effects on sleep quality. Therefore, in the present study, we sought to investigate the effects of Eye Movement Desensitization Reprocessing therapy on indices of mood, anxiety, subjective, and objective sleep. The sample was composed of 11 healthy controls and 13 PTSD patients that were victims of assault and/or kidnapping. All participants were assessed before, and 1 day after, the end of treatment for depressive and anxiety profile, general well-being and subjective sleep by filling out specific questionnaires. In addition, objective sleep patterns were evaluated by polysomnographic recording. Healthy volunteers were submitted to the therapy for three weekly sessions, whereas PTSD patients underwent five sessions, on average. Before treatment, PTSD patients exhibited high levels of anxiety and depression, poor quality of life and poor sleep, assessed both subjectively and objectively; the latter was reflected by increased time of waking after sleep onset. After completion of treatment, patients exhibited improvement in depression and anxiety symptoms, and in quality of life; with indices that were no longer different from control volunteers. Moreover, these patients showed more consolidated sleep, with reduction of time spent awake after sleep onset. In conclusion, Eye Movement Desensitization and Reprocessing was an effective treatment of PTSD patients and improved the associated sleep and psychological symptoms. PMID:24959123

  15. Factitious posttraumatic stress disorder.

    PubMed

    Sparr, L; Pankratz, L D

    1983-08-01

    A growing number of young men have reported an array of symptoms that suggest a diagnosis of posttraumatic stress disorder. Five such men, all claiming to be Viet Nam veterans, were treated at a VA medical center; three said they were former prisoners of war. In fact, none had been prisoners of war, four had never been in Viet Nam, and two had never even been in the military. Instead, all five suffered factitious disorders. The authors describe the five patients and discuss differential diagnoses; the value of verifying military histories is stressed.

  16. Stress and Sleep Disorder

    PubMed Central

    Han, Kuem Sun; Kim, Lin

    2012-01-01

    The purpose of this study was to review potential, physiological, hormonal and neuronal mechanisms that may mediate the sleep changes. This paper investigates the literatures regarding the activity of the hypothalamic-pituitary-adrenal (HPA) axis, one of the main neuroendocrine stress systems during sleep in order to identify relations between stress and sleep disorder and the treatment of stress-induced insomnia. Sleep and wakefulness are regulated by the aminergic, cholinergic brainstem and hypothalamic systems. Activation of the HPA and/or the sympathetic nervous systems results in wakefulness and these hormones including corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), cortisol or corticosterone, noradrenaline, and adrenaline, are associated with attention and arousal. Stress-related insomnia leads to a vicious circle by activating the HPA system. An awareness of the close interaction between sleep and stress systems is emerging and the hypothalamus is now recognized as a key center for sleep regulation, with hypothalamic neurontransmitter systems providing the framework for therapeutic advances. An updated understanding of these systems may allow researchers to elucidate neural mechanisms of sleep disorder and to develop effective intervention for sleep disorder. PMID:23319874

  17. Does pediatric post-traumatic stress disorder alter the brain? Systematic review and meta-analysis of structural and functional magnetic resonance imaging studies.

    PubMed

    Milani, Ana Carolina C; Hoffmann, Elis V; Fossaluza, Victor; Jackowski, Andrea P; Mello, Marcelo F

    2017-03-01

    Several studies have recently demonstrated that the volumes of specific brain regions are reduced in children and adolescents with post-traumatic stress disorder (PTSD) compared with those of healthy controls. Our study investigated the potential association between early traumatic experiences and altered brain regions and functions. We conducted a systematic review of the scientific literature regarding functional magnetic resonance imaging and a meta-analysis of structural magnetic resonance imaging studies that investigated cerebral region volumes in pediatric patients with PTSD. We searched for articles from 2000 to 2014 in the PsycINFO, PubMed, Medline, Lilacs, and ISI (Web of Knowledge) databases. All data regarding the amygdala, hippocampus, corpus callosum, brain, and intracranial volumes that fit the inclusion criteria were extracted and combined in a meta-analysis that assessed differences between groups. The meta-analysis found reduced total corpus callosum areas and reduced total cerebral and intracranial volumes in the patients with PTSD. The total hippocampus (left and right hippocampus) and gray matter volumes of the amygdala and frontal lobe were also reduced, but these differences were not significant. The functional studies revealed differences in brain region activation in response to stimuli in the post-traumatic stress symptoms/PTSD group. Our results confirmed that the pediatric patients with PTSD exhibited structural and functional brain abnormalities and that some of the abnormalities occurred in different brain regions than those observed in adults. © 2016 The Authors. Psychiatry and Clinical Neurosciences © 2016 Japanese Society of Psychiatry and Neurology.

  18. Epigenetic Alterations in Muscular Disorders

    PubMed Central

    Lanzuolo, Chiara

    2012-01-01

    Epigenetic mechanisms, acting via chromatin organization, fix in time and space different transcriptional programs and contribute to the quality, stability, and heritability of cell-specific transcription programs. In the last years, great advances have been made in our understanding of mechanisms by which this occurs in normal subjects. However, only a small part of the complete picture has been revealed. Abnormal gene expression patterns are often implicated in the development of different diseases, and thus epigenetic studies from patients promise to fill an important lack of knowledge, deciphering aberrant molecular mechanisms at the basis of pathogenesis and diseases progression. The identification of epigenetic modifications that could be used as targets for therapeutic interventions could be particularly timely in the light of pharmacologically reversion of pathological perturbations, avoiding changes in DNA sequences. Here I discuss the available information on epigenetic mechanisms that, altered in neuromuscular disorders, could contribute to the progression of the disease. PMID:22761545

  19. Chronic Stress and Posttraumatic Stress Disorders.

    ERIC Educational Resources Information Center

    Davidson, Laura M.; Baum, Andrew

    1986-01-01

    Examined the relationship between chronic stress and symptoms of posttraumatic stress syndrome in people living within five miles of the Three Mile Island (TMI) nuclear power station. Results provided evidence of substantive links between chronic stress and development of mild symptoms of posttraumatic stress disorder. (Author/BL)

  20. Brain and behavioral evidence for altered social learning mechanisms among women with assault-related posttraumatic stress disorder.

    PubMed

    Cisler, Josh M; Bush, Keith; Scott Steele, J; Lenow, Jennifer K; Smitherman, Sonet; Kilts, Clinton D

    2015-04-01

    Current neurocircuitry models of PTSD focus on the neural mechanisms that mediate hypervigilance for threat and fear inhibition/extinction learning. Less focus has been directed towards explaining social deficits and heightened risk of revictimization observed among individuals with PTSD related to physical or sexual assault. The purpose of the present study was to foster more comprehensive theoretical models of PTSD by testing the hypothesis that assault-related PTSD is associated with behavioral impairments in a social trust and reciprocity task and corresponding alterations in the neural encoding of social learning mechanisms. Adult women with assault-related PTSD (n = 25) and control women (n = 15) completed a multi-trial trust game outside of the MRI scanner. A subset of these participants (15 with PTSD and 14 controls) also completed a social and non-social reinforcement learning task during 3T fMRI. Brain regions that encoded the computationally modeled parameters of value expectation, prediction error, and volatility (i.e., uncertainty) were defined and compared between groups. The PTSD group demonstrated slower learning rates during the trust game and social prediction errors had a lesser impact on subsequent investment decisions. PTSD was also associated with greater encoding of negative expected social outcomes in perigenual anterior cingulate cortex and bilateral middle frontal gyri, and greater encoding of social prediction errors in the left temporoparietal junction. These data suggest mechanisms of PTSD-related deficits in social functioning and heightened risk for re-victimization in assault victims; however, comorbidity in the PTSD group and the lack of a trauma-exposed control group temper conclusions about PTSD specifically.

  1. Brain and Behavioral Evidence for Altered Social Learning Mechanisms among Women with Assault-Related Posttraumatic Stress Disorder

    PubMed Central

    Cisler, Josh M.; Bush, Keith; Steele, J. Scott; Lenow, Jennifer K.; Smitherman, Sonet; Kilts, Clinton D.

    2015-01-01

    Current neurocircuitry models of PTSD focus on the neural mechanisms that mediate hypervigilance for threat and fear inhibition/extinction learning. Less focus has been directed towards explaining social deficits and heightened risk of revictimization observed among individuals with PTSD related to physical or sexual assault. The purpose of the present study was to foster more comprehensive theoretical models of PTSD by testing the hypothesis that assault-related PTSD is associated with behavioral impairments in a social trust and reciprocity task and corresponding alterations in the neural encoding of social learning mechanisms. Adult women with assault-related PTSD (n=25) and control women (n=15) completed a multi-trial trust game outside of the MRI scanner. A subset of these participants (15 with PTSD and 14 controls) also completed a social and non-social reinforcement learning task during 3T fMRI. Brain regions that encoded the computationally modeled parameters of value expectation, prediction error, and volatility (i.e., uncertainty) were defined and compared between groups. The PTSD group demonstrated slower learning rates during the trust game and social prediction errors had a lesser impact on subsequent investment decisions. PTSD was also associated with greater encoding of negative expected social outcomes in perigenual anterior cingulate cortex and bilateral middle frontal gyri, and greater encoding of social prediction errors in the left temporoparietal junction. These data suggest mechanisms of PTSD-related deficits in social functioning and heightened risk for re-victimization in assault victims; however, comorbidity in the PTSD group and the lack of a trauma-exposed control group temper conclusions about PTSD specifically. PMID:25769397

  2. Dysregulation in microRNA Expression Is Associated with Alterations in Immune Functions in Combat Veterans with Post-Traumatic Stress Disorder

    PubMed Central

    Zhou, Juhua; Nagarkatti, Prakash; Zhong, Yin; Ginsberg, Jay P.; Singh, Narendra P.; Zhang, Jiajia; Nagarkatti, Mitzi

    2014-01-01

    While the immunological dysfunction in combat Veterans with post-traumatic stress disorder (PTSD) has been well documented, the precise mechanisms remain unclear. The current study evaluated the role of microRNA (miR) in immunological dysfunction associated with PTSD. The presence of peripheral blood mononuclear cells (PBMC) and various lymphocyte subsets in blood collected from PTSD patients were analyzed. Our studies demonstrated that the numbers of both PBMC and various lymphocyte subsets increased significantly in PTSD patients. When T cells were further analyzed, the percentage of Th1 cells and Th17 cells increased, regulatory T cells(Tregs) decreased, while Th2 cells remained unaltered in PTSD patients. These data correlated with increased plasma levels of IFN-γ and IL-17 while IL-4 showed no significant change. The increase in PBMC counts, Th1 and Th17 cells seen in PTSD patients correlated with the clinical scores. High-throughput analysis of PBMCs for 1163 miRs showed that the expression of a significant number of miRs was altered in PTSD patients. Pathway analysis of dysregulated miRs seen in PTSD patients revealed relationship between selected miRNAs and genes that showed direct/indirect role in immunological signaling pathways consistent with the immunological changes seen in these patients. Of interest was the down-regulation of miR-125a in PTSD, which specifically targeted IFN-γ production. Together, the current study demonstrates for the first time that PTSD was associated with significant alterations in miRNAs, which may promote pro-inflammatory cytokine profile. Such epigenetic events may provide useful tools to identify potential biomarkers for diagnosis, and facilitate therapy of PTSD. PMID:24759737

  3. Oxidative Stress and Psychological Disorders

    PubMed Central

    Salim, Samina

    2014-01-01

    Oxidative stress is an imbalance between cellular production of reactive oxygen species and the counteracting antioxidant mechanisms. The brain with its high oxygen consumption and a lipid-rich environment is considered highly susceptible to oxidative stress or redox imbalances. Therefore, the fact that oxidative stress is implicated in several mental disorders including depression, anxiety disorders, schizophrenia and bipolar disorder, is not surprising. Although several elegant studies have established a link between oxidative stress and psychiatric disorders, the causal relationship between oxidative stress and psychiatric diseases is not fully determined. Another critical aspect that needs much attention and effort is our understanding of the association between cellular oxidative stress and emotional stress. This review examines some of the recent discoveries that link oxidative status with anxiety, depression, schizophrenia and bipolar disorder. A discussion of published results and questions that currently exist in the field regarding a causal relationship between oxidative and emotional stress is also provided. PMID:24669208

  4. Chronic Unpredictable Stress (CUS)-Induced Anxiety and Related Mood Disorders in a Zebrafish Model: Altered Brain Proteome Profile Implicates Mitochondrial Dysfunction

    PubMed Central

    Chakravarty, Sumana; Reddy, Bommana R.; Sudhakar, Sreesha R.; Saxena, Sandeep; Das, Tapatee; Meghah, Vuppalapaty; Brahmendra Swamy, Cherukuvada V.; Kumar, Arvind; Idris, Mohammed M.

    2013-01-01

    Anxiety and depression are major chronic mood disorders, and the etiopathology for each appears to be repeated exposure to diverse unpredictable stress factors. Most of the studies on anxiety and related mood disorders are performed in rodents, and a good model is chronic unpredictable stress (CUS). In this study, we have attempted to understand the molecular basis of the neuroglial and behavioral changes underlying CUS-induced mood disorders in the simplest vertebrate model, the zebrafish, Danio rerio. Zebrafish were subjected to a CUS paradigm in which two different stressors were used daily for 15 days, and thorough behavioral analyses were performed to assess anxiety and related mood disorder phenotypes using the novel tank test, shoal cohesion and scototaxis. Fifteen days of exposure to chronic stressors appears to induce an anxiety and related mood disorder phenotype. Decreased neurogenesis, another hallmark of anxiety and related disorders in rodents, was also observed in this zebrafish model. The common molecular markers of rodent anxiety and related disorders, corticotropin-releasing factor (CRF), calcineurin (ppp3r1a) and phospho cyclic AMP response element binding protein (pCREB), were also replicated in the fish model. Finally, using 2DE FTMS/ITMSMS proteomics analyses, 18 proteins were found to be deregulated in zebrafish anxiety and related disorders. The most affected process was mitochondrial function, 4 of the 18 differentially regulated proteins were mitochondrial proteins: PHB2, SLC25A5, VDAC3 and IDH2, as reported in rodent and clinical samples. Thus, the zebrafish CUS model and proteomics can facilitate not only uncovering new molecular targets of anxiety and related mood disorders but also the routine screening of compounds for drug development. PMID:23691016

  5. Chronic unpredictable stress (CUS)-induced anxiety and related mood disorders in a zebrafish model: altered brain proteome profile implicates mitochondrial dysfunction.

    PubMed

    Chakravarty, Sumana; Reddy, Bommana R; Sudhakar, Sreesha R; Saxena, Sandeep; Das, Tapatee; Meghah, Vuppalapaty; Brahmendra Swamy, Cherukuvada V; Kumar, Arvind; Idris, Mohammed M

    2013-01-01

    Anxiety and depression are major chronic mood disorders, and the etiopathology for each appears to be repeated exposure to diverse unpredictable stress factors. Most of the studies on anxiety and related mood disorders are performed in rodents, and a good model is chronic unpredictable stress (CUS). In this study, we have attempted to understand the molecular basis of the neuroglial and behavioral changes underlying CUS-induced mood disorders in the simplest vertebrate model, the zebrafish, Danio rerio. Zebrafish were subjected to a CUS paradigm in which two different stressors were used daily for 15 days, and thorough behavioral analyses were performed to assess anxiety and related mood disorder phenotypes using the novel tank test, shoal cohesion and scototaxis. Fifteen days of exposure to chronic stressors appears to induce an anxiety and related mood disorder phenotype. Decreased neurogenesis, another hallmark of anxiety and related disorders in rodents, was also observed in this zebrafish model. The common molecular markers of rodent anxiety and related disorders, corticotropin-releasing factor (CRF), calcineurin (ppp3r1a) and phospho cyclic AMP response element binding protein (pCREB), were also replicated in the fish model. Finally, using 2DE FTMS/ITMSMS proteomics analyses, 18 proteins were found to be deregulated in zebrafish anxiety and related disorders. The most affected process was mitochondrial function, 4 of the 18 differentially regulated proteins were mitochondrial proteins: PHB2, SLC25A5, VDAC3 and IDH2, as reported in rodent and clinical samples. Thus, the zebrafish CUS model and proteomics can facilitate not only uncovering new molecular targets of anxiety and related mood disorders but also the routine screening of compounds for drug development.

  6. Early Life Stress, Mood, and Anxiety Disorders.

    PubMed

    Syed, Shariful A; Nemeroff, Charles B

    2017-02-01

    Early life stress has been shown to exert profound short- and long-term effects on human physiology both in the central nervous system and peripherally. Early life stress has demonstrated clear association with many psychiatric disorders including major depression, posttraumatic stress disorder, and bipolar disorder. The Diagnostic and Statistics Manuel of Mental Disorders (DSM) diagnostic categorical system has served as a necessary framework for clinical service, delivery, and research, however has not been completely matching the neurobiological research perspective. Early life stress presents a complex dynamic featuring a wide spectrum of physiologic alterations: from epigenetic alterations, inflammatory changes, to dysregulation of the hypothalamic pituitary axis and has further added to the challenge of identifying biomarkers associated with psychiatric disorders. The National Institute of Mental Health's proposed Research Domain Criteria initiative incorporates a dimensional approach to assess discrete domains and constructs of behavioral function that are subserved by identifiable neural circuits. The current neurobiology of early life stress is reviewed in accordance with dimensional organization of Research Domain Criteria matrix and how the findings as a whole fit within the Research Domain Criteria frameworks.

  7. Does prenatal stress alter the developing connectome?

    PubMed Central

    Scheinost, Dustin; Sinha, Rajita; Cross, Sarah N.; Kwon, Soo Hyun; Sze, Gordon; Constable, R. Todd; Ment, Laura R.

    2017-01-01

    Human neurodevelopment requires the organization of neural elements into complex structural and functional networks called the connectome. Emerging data suggest that prenatal exposure to maternal stress plays a role in the wiring, or miswiring, of the developing connectome. Stress-related symptoms are common in women during pregnancy and are risk factors for neurobehavioral disorders ranging from autism spectrum disorder, attention deficit hyperactivity disorder, and addiction, to major depression and schizophrenia. This review focuses on structural and functional connectivity imaging to assess the impact of changes in women's stress-based physiology on the dynamic development of the human connectome in the fetal brain. PMID:27673421

  8. Does prenatal stress alter the developing connectome?

    PubMed

    Scheinost, Dustin; Sinha, Rajita; Cross, Sarah N; Kwon, Soo Hyun; Sze, Gordon; Constable, R Todd; Ment, Laura R

    2017-01-01

    Human neurodevelopment requires the organization of neural elements into complex structural and functional networks called the connectome. Emerging data suggest that prenatal exposure to maternal stress plays a role in the wiring, or miswiring, of the developing connectome. Stress-related symptoms are common in women during pregnancy and are risk factors for neurobehavioral disorders ranging from autism spectrum disorder, attention deficit hyperactivity disorder, and addiction, to major depression and schizophrenia. This review focuses on structural and functional connectivity imaging to assess the impact of changes in women's stress-based physiology on the dynamic development of the human connectome in the fetal brain.

  9. Prenatal stress alters amygdala functional connectivity in preterm neonates.

    PubMed

    Scheinost, Dustin; Kwon, Soo Hyun; Lacadie, Cheryl; Sze, Gordon; Sinha, Rajita; Constable, R Todd; Ment, Laura R

    2016-01-01

    Exposure to prenatal and early-life stress results in alterations in neural connectivity and an increased risk for neuropsychiatric disorders. In particular, alterations in amygdala connectivity have emerged as a common effect across several recent studies. However, the impact of prenatal stress exposure on the functional organization of the amygdala has yet to be explored in the prematurely-born, a population at high risk for neuropsychiatric disorders. We test the hypothesis that preterm birth and prenatal exposure to maternal stress alter functional connectivity of the amygdala using two independent cohorts. The first cohort is used to establish the effects of preterm birth and consists of 12 very preterm neonates and 25 term controls, all without prenatal stress exposure. The second is analyzed to establish the effects of prenatal stress exposure and consists of 16 extremely preterm neonates with prenatal stress exposure and 10 extremely preterm neonates with no known prenatal stress exposure. Standard resting-state functional magnetic resonance imaging and seed connectivity methods are used. When compared to term controls, very preterm neonates show significantly reduced connectivity between the amygdala and the thalamus, the hypothalamus, the brainstem, and the insula (p < 0.05). Similarly, when compared to extremely preterm neonates without exposure to prenatal stress, extremely preterm neonates with exposure to prenatal stress show significantly less connectivity between the left amygdala and the thalamus, the hypothalamus, and the peristriate cortex (p < 0.05). Exploratory analysis of the combined cohorts suggests additive effects of prenatal stress on alterations in amygdala connectivity associated with preterm birth. Functional connectivity from the amygdala to other subcortical regions is decreased in preterm neonates compared to term controls. In addition, these data, for the first time, suggest that prenatal stress exposure amplifies these

  10. Posttraumatic stress disorder: A metabolic disorder in disguise?

    PubMed

    Michopoulos, Vasiliki; Vester, Aimee; Neigh, Gretchen

    2016-10-01

    Posttraumatic stress disorder (PTSD) is a heterogeneous psychiatric disorder that affects individuals exposed to trauma and is highly co-morbid with other adverse health outcomes, including cardiovascular disease and obesity. The unique pathophysiological feature of PTSD is the inability to inhibit fear responses, such that individuals suffering from PTSD re-experience traumatic memories and are unable to control psychophysiological responses to trauma-associated stimuli. However, underlying alterations in sympathetic nervous system activity, neuroendocrine systems, and metabolism associated with PTSD are similar to those present in traditional metabolic disorders, such as obesity and diabetes. The current review highlights existing clinical, translational, and preclinical data that support the notion that underneath the primary indication of impaired fear inhibition, PTSD is itself also a metabolic disorder and proposes altered function of inflammatory responses as a common underlying mechanism. The therapeutic implications of treating PTSD as a whole-body condition are significant, as targeting any underlying biological system whose activity is altered in both PTSD and metabolic disorders, (i.e. HPA axis, sympathetic nervous systems, inflammation) may elicit symptomatic relief in individuals suffering from these whole-body adverse outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Posttraumatic Stress Disorder

    MedlinePlus

    ... that can cause PTSD include: violent assaults, including rape fire physical or sexual abuse acts of violence ( ... Mental Health Care Coping With Stressful Situations Date Rape Suicide Rape Contact Us Print Resources Send to ...

  12. Psychoneuroendocrinology of post-traumatic stress disorder.

    PubMed

    Yehuda, R

    1998-06-01

    In 1980, the diagnosis of post-traumatic stress disorder (PTSD) was established to describe the long-lasting symptoms that can occur following exposure to extremely stressful life events. This article reviews the findings of neuroendocrinologic alterations in PTSD and summarizes the finding of hypothalamic-pituitary-adrenal (HPA), catecholamine, hypothalamic-pituitary-thyroid (HPT) and hypothalamic-pituitary-gonadal (HPG) systems. These are the neuroendocrine systems that have been studied in PTSD. Also included is a review of the basic facts about PTSD and biologic data.

  13. Oxidative stress markers in affective disorders.

    PubMed

    Siwek, Marcin; Sowa-Kućma, Magdalena; Dudek, Dominika; Styczeń, Krzysztof; Szewczyk, Bernadeta; Kotarska, Katarzyna; Misztakk, Paulina; Pilc, Agnieszka; Wolak, Małgorzata; Nowak, Gabriel

    2013-01-01

    Affective disorders are a medical condition with a complex biological pattern of etiology, involving genetic and epigenetic factors, along with different environmental stressors. Increasing numbers of studies indicate that induction of oxidative and nitrosative stress (O&NS) pathways, which is accompanied by immune-inflammatory response, might play an important role in the pathogenic mechanisms underlying many major psychiatric disorders, including depression and bipolar disorder. Reactive oxygen and nitrogen species have been shown to impair the brain function by modulating activity of principal neurotransmitter (e.g., glutamatergic) systems involved in the neurobiology of depression. Both preclinical and clinical studies revealed that depression is associated with altered levels of oxidative stress markers and typically reduced concentrations of several endogenous antioxidant compounds, such as glutathione, vitamin E, zinc and coenzyme Q10, or enzymes, including glutathione peroxidase, and with an impairment of the total antioxidant status. These oxidative stress parameters can be normalized by successful antidepressant therapy. On the other hand, some antioxidants (zinc, N-acetylcysteine, omega-3 free fatty acids) may exhibit antidepressant properties or enhance standard antidepressant therapy. These observations introduce new potential targets for the development of therapeutic interventions based on antioxidant compounds. The present paper reviews selected animal and human studies providing evidence that oxidative stress is implicated in the pathophysiology and treatment of depression and bipolar disorder.

  14. Posttraumatic Stress Disorder (PTSD) and Stress Related Disorders

    PubMed Central

    Shalev, Arieh Y.

    2009-01-01

    Synopsis Post-traumatic Stress Disorder (PTSD) is a prevalent anxiety disorder. PTSD typically follows a psychologically traumatic event, and thus has a recognizable point of onset. PTSD symptoms are present shortly after an exposure to a traumatic event, abate with time in the majority of those who initially express them, and leave a significant minority with chronic PTSD. PTSD may be treated with pharmacotherapy or psychotherapy. The treatment of the early expressions of disorder constitutes a separate domain of theory and research. The treatment of chronic PTSD often stabilizes the condition, but rarely produces stable remission. This chapter reviews the empirical evidence on the treatment of acute and chronic PTSD, outlines similarities and differences between PTSD and other Axis I disorders, evaluates new therapeutic approaches, and discusses the implications of current knowledge for the forthcoming DSM V. PMID:19716997

  15. Chronic social stress leads to altered sleep homeostasis in mice.

    PubMed

    Olini, Nadja; Rothfuchs, Iru; Azzinnari, Damiano; Pryce, Christopher R; Kurth, Salome; Huber, Reto

    2017-03-15

    Disturbed sleep and altered sleep homeostasis are core features of many psychiatric disorders such as depression. Chronic uncontrollable stress is considered an important factor in the development of depression, but little is known on how chronic stress affects sleep regulation and sleep homeostasis. We therefore examined the effects of chronic social stress (CSS) on sleep regulation in mice. Adult male C57BL/6 mice were implanted for electrocortical recordings (ECoG) and underwent either a 10-day CSS protocol or control handling (CON). Subsequently, ECoG was assessed across a 24-h post-stress baseline, followed by a 4-h sleep deprivation, and then a 20-h recovery period. After sleep deprivation, CSS mice showed a blunted increase in sleep pressure compared to CON mice, as measured using slow wave activity (SWA, electroencephalographic power between 1 - 4Hz) during non-rapid eye movement (NREM) sleep. Vigilance states did not differ between CSS and CON mice during post-stress baseline, sleep deprivation or recovery, with the exception of CSS mice exhibiting increased REM sleep during recovery sleep. Behavior during sleep deprivation was not affected by CSS. Our data provide evidence that CSS alters the homeostatic regulation of sleep SWA in mice. In contrast to acute social stress, which results in a faster SWA build-up, CSS decelerates the homeostatic build up. These findings are discussed in relation to the causal contribution of stress-induced sleep disturbance to depression.

  16. Childhood stressful events, HPA axis and anxiety disorders.

    PubMed

    Faravelli, Carlo; Lo Sauro, Carolina; Godini, Lucia; Lelli, Lorenzo; Benni, Laura; Pietrini, Francesco; Lazzeretti, Lisa; Talamba, Gabriela Alina; Fioravanti, Giulia; Ricca, Valdo

    2012-02-22

    Anxiety disorders are among the most common of all mental disorders and their pathogenesis is a major topic in psychiatry, both for prevention and treatment. Early stressful life events and alterations of hypothalamic pituitary adrenal (HPA) axis function seem to have a significant role in the onset of anxiety. Existing data appear to support the mediating effect of the HPA axis between childhood traumata and posttraumatic stress disorder. Findings on the HPA axis activity at baseline and after stimuli in panic disordered patients are inconclusive, even if stressful life events may have a triggering function in the development of this disorder. Data on the relationship between stress, HPA axis functioning and obsessive-compulsive disorder (OCD) are scarce and discordant, but an increased activity of the HPA axis is reported in OCD patients. Moreover, normal basal cortisol levels and hyper-responsiveness of the adrenal cortex during a psychosocial stressor are observed in social phobics. Finally, abnormal HPA axis activity has also been observed in generalized anxiety disordered patients. While several hypothesis have attempted to explain these findings over time, currently the most widely accepted theory is that early stressful life events may provoke alterations of the stress response and thus of the HPA axis, that can endure during adulthood, predisposing individuals to develop psychopathology. All theories are reviewed and the authors conclude that childhood life events and HPA abnormalities may be specifically and transnosographically related to all anxiety disorders, as well as, more broadly, to all psychiatric disorders.

  17. Altered gene expression of the innate immune, neuroendocrine, and nuclear factor-kappa B (NF-κB) systems is associated with posttraumatic stress disorder in military personnel.

    PubMed

    Guardado, Pedro; Olivera, Anlys; Rusch, Heather L; Roy, Michael; Martin, Christiana; Lejbman, Natasha; Lee, Hwyunhwa; Gill, Jessica M

    2016-03-01

    Whole transcriptome analysis provides an unbiased examination of biological activity, and likely, unique insight into the mechanisms underlying posttraumatic stress disorder (PTSD) and comorbid depression and traumatic brain injury. This study compared gene-expression profiles in military personnel with PTSD (n=28) and matched controls without PTSD (n=27) using HG-U133 Plus 2.0 microarrays (Affymetrix), which contain 54,675 probe sets representing more than 38,500 genes. Analysis of expression profiles revealed 203 differentially expressed genes in PTSD, of which 72% were upregulated. Using Partek Genomics Suite 6.6, differentially expressed transcription clusters were filtered based on a selection criterion of ≥1.5 relative fold change at a false discovery rate of ≤5%. Ingenuity Pathway Analysis (Qiagen) of the differentially expressed genes indicated a dysregulation of genes associated with the innate immune, neuroendocrine, and NF-κB systems. These findings provide novel insights that may lead to new pharmaceutical agents for PTSD treatments and help mitigate mental and physical comorbidity risk.

  18. Altered Emotion Perception in Insomnia Disorder

    PubMed Central

    Kyle, Simon D.; Beattie, Louise; Spiegelhalder, Kai; Rogers, Zoe; Espie, Colin A.

    2014-01-01

    Study Objectives: Chronic insomnia is a prevalent sleep disorder that negatively affects daytime functioning and confers risk for the future development of psychiatric disorder. Patients with insomnia often report problems with emotion regulation and impaired social interactions. Moreover, experimental sleep loss in healthy adults is associated with altered reactivity to and interpretation of emotional information. In the current study, we investigated socioemotional processing in patients with chronic insomnia disorder relative to healthy good sleepers. Design: Between-groups comparison. Setting: Sleep Research Laboratory. Participants: Patients with well-defined psychophysiological insomnia (PI; n = 16), free from psychiatric disorder, and an age- and sex-matched control group of good sleepers (GS; n = 15). Interventions: N/A. Measurement and Results: All participants completed a facial expression recognition task, between 18:00 and 19:00, requiring participants to categorize and rate the intensity of four emotional expression categories: anger, fear, happiness, and sadness. People with PI did not differ from GS with respect to categorization of facial expressions. However, in terms of intensity judgements, across all emotion categories, patients tended to rate faces as less emotionally intense (Cohen's d = 0.70). Specifically, they rated expressions displaying sadness and fear as significantly less emotionally intense than healthy GS (both P < 0.05; Cohen's d = 0.77 and 0.89, respectively). Measures of sleepiness (Psychomotor Vigilance Test, Karolinska Sleepiness Scale) or self-reported sleep were not reliably associated with emotional intensity ratings. However, anxiety and depression were negatively related to intensity ratings. Conclusion: For the first time we show that chronic insomnia is associated with reduced ratings of emotion intensity for face expressions displaying sadness and fear. Further work is required to elucidate possible mechanisms and

  19. ALTERED DEFAULT MODE NETWORK (DMN) RESTING STATE FUNCTIONAL CONNECTIVITY FOLLOWING A MINDFULNESS-BASED EXPOSURE THERAPY FOR POSTTRAUMATIC STRESS DISORDER (PTSD) IN COMBAT VETERANS OF AFGHANISTAN AND IRAQ.

    PubMed

    King, Anthony P; Block, Stefanie R; Sripada, Rebecca K; Rauch, Sheila; Giardino, Nicholas; Favorite, Todd; Angstadt, Michael; Kessler, Daniel; Welsh, Robert; Liberzon, Israel

    2016-04-01

    Recent studies suggest that mindfulness may be an effective component for posttraumatic stress disorder (PTSD) treatment. Mindfulness involves practice in volitional shifting of attention from "mind wandering" to present-moment attention to sensations, and cultivating acceptance. We examined potential neural correlates of mindfulness training using a novel group therapy (mindfulness-based exposure therapy (MBET)) in combat veterans with PTSD deployed to Afghanistan (OEF) and/or Iraq (OIF). Twenty-three male OEF/OIF combat veterans with PTSD were treated with a mindfulness-based intervention (N = 14) or an active control group therapy (present-centered group therapy (PCGT), N = 9). Pre-post therapy functional magnetic resonance imaging (fMRI, 3 T) examined resting-state functional connectivity (rsFC) in default mode network (DMN) using posterior cingulate cortex (PCC) and ventral medial prefrontal cortex (vmPFC) seeds, and salience network (SN) with anatomical amygdala seeds. PTSD symptoms were assessed at pre- and posttherapy with Clinician Administered PTSD Scale (CAPS). Patients treated with MBET had reduced PTSD symptoms (effect size d = 0.92) but effect was not significantly different from PCGT (d = 0.46). Increased DMN rsFC (PCC seed) with dorsolateral dorsolateral prefrontal cortex (DLPFC) regions and dorsal anterior cingulate cortex (ACC) regions associated with executive control was seen following MBET. A group × time interaction found MBET showed increased connectivity with DLPFC and dorsal ACC following therapy; PCC-DLPFC connectivity was correlated with improvement in PTSD avoidant and hyperarousal symptoms. Increased connectivity between DMN and executive control regions following mindfulness training could underlie increased capacity for volitional shifting of attention. The increased PCC-DLPFC rsFC following MBET was related to PTSD symptom improvement, pointing to a potential therapeutic mechanism of mindfulness-based therapies. © 2016 Wiley

  20. Gas exchange under altered gravitational stress.

    PubMed

    Prisk, G Kim

    2011-01-01

    Efficient gas exchange in the lung depends on the matching of ventilation and perfusion. However, the human lung is a readily deformable structure and as a result gravitational stresses generate gradients in both ventilation and perfusion. Nevertheless, the lung is capable of withstanding considerable change in the applied gravitational load before pulmonary gas exchange becomes impaired. The postural changes that are part of the everyday existence for most bipedal species are well tolerated, as is the removal of gravity (weightlessness). Increases in the applied gravitational load result only in a large impairment in pulmonary gas exchange above approximately three times that on the ground, at which point the matching of ventilation to perfusion is so impaired that efficient gas exchange is no longer possible. Much of the tolerance of the lung to alterations in gravitation stress comes from the fact that ventilation and perfusion are inextricably coupled. Deformations in the lung that alter ventilation necessarily alter perfusion, thus maintaining a degree of matching and minimizing the disruption in ventilation to perfusion ratio and thus gas exchange.

  1. Unpredictable Chronic Stress Alters Adenosine Metabolism in Zebrafish Brain.

    PubMed

    Zimmermann, F F; Altenhofen, S; Kist, L W; Leite, C E; Bogo, M R; Cognato, G P; Bonan, C D

    2016-05-01

    Stress is considered a risk factor for several human disorders. Despite the broad knowledge of stress responses in mammals, data on the relationship between unpredictable chronic stress (UCS) and its effects on purinergic signaling are limited. ATP hydrolysis by ectonucleotidases is an important source of adenosine, and adenosine deaminase (ADA) contributes to the control of the nucleoside concentrations. Considering that some stress models could affect signaling systems, the objective of this study was to investigate whether UCS alters ectonucleotidase and ADA pathway in zebrafish brain. Additionally, we analyzed ATP metabolism as well as ada1, ada2.1, ada2.2, adaL, and adaasi gene expression in zebrafish brain. Our results have demonstrated that UCS did not alter ectonucleotidase and soluble ADA activities. However, ecto-ADA activity was significantly decreased (26.8%) in brain membranes of animals exposed to UCS when compared to the control group. Quantitative reverse transcription PCR (RT-PCR) analysis did not show significant changes on ADA gene expression after the UCS exposure. The brain ATP metabolism showed a marked increase in adenosine levels (ADO) in animals exposed to UCS. These data suggest an increase on extracellular adenosine levels in zebrafish brain. Since this nucleoside has neuromodulatory and anxiolytic effects, changes in adenosine levels could play a role in counteracting the stress, which could be related to a compensatory mechanism in order to restore the homeostasis.

  2. Post-traumatic stress disorder.

    PubMed

    Yehuda, Rachel; Hoge, Charles W; McFarlane, Alexander C; Vermetten, Eric; Lanius, Ruth A; Nievergelt, Caroline M; Hobfoll, Stevan E; Koenen, Karestan C; Neylan, Thomas C; Hyman, Steven E

    2015-10-08

    Post-traumatic stress disorder (PTSD) occurs in 5-10% of the population and is twice as common in women as in men. Although trauma exposure is the precipitating event for PTSD to develop, biological and psychosocial risk factors are increasingly viewed as predictors of symptom onset, severity and chronicity. PTSD affects multiple biological systems, such as brain circuitry and neurochemistry, and cellular, immune, endocrine and metabolic function. Treatment approaches involve a combination of medications and psychotherapy, with psychotherapy overall showing greatest efficacy. Studies of PTSD pathophysiology initially focused on the psychophysiology and neurobiology of stress responses, and the acquisition and the extinction of fear memories. However, increasing emphasis is being placed on identifying factors that explain individual differences in responses to trauma and promotion of resilience, such as genetic and social factors, brain developmental processes, cumulative biological and psychological effects of early childhood and other stressful lifetime events. The field of PTSD is currently challenged by fluctuations in diagnostic criteria, which have implications for epidemiological, biological, genetic and treatment studies. However, the advent of new biological methodologies offers the possibility of large-scale approaches to heterogeneous and genetically complex brain disorders, and provides optimism that individualized approaches to diagnosis and treatment will be discovered.

  3. The neurobiology of oppositional defiant disorder and conduct disorder: altered functioning in three mental domains.

    PubMed

    Matthys, Walter; Vanderschuren, Louk J M J; Schutter, Dennis J L G

    2013-02-01

    This review discusses neurobiological studies of oppositional defiant disorder and conduct disorder within the conceptual framework of three interrelated mental domains: punishment processing, reward processing, and cognitive control. First, impaired fear conditioning, reduced cortisol reactivity to stress, amygdala hyporeactivity to negative stimuli, and altered serotonin and noradrenaline neurotransmission suggest low punishment sensitivity, which may compromise the ability of children and adolescents to make associations between inappropriate behaviors and forthcoming punishments. Second, sympathetic nervous system hyporeactivity to incentives, low basal heart rate associated with sensation seeking, orbitofrontal cortex hyporeactiviy to reward, and altered dopamine functioning suggest a hyposensitivity to reward. The associated unpleasant emotional state may make children and adolescents prone to sensation-seeking behavior such as rule breaking, delinquency, and substance abuse. Third, impairments in executive functions, especially when motivational factors are involved, as well as structural deficits and impaired functioning of the paralimbic system encompassing the orbitofrontal and cingulate cortex, suggest impaired cognitive control over emotional behavior. In the discussion we argue that more insight into the neurobiology of oppositional defiance disorder and conduct disorder may be obtained by studying these disorders separately and by paying attention to the heterogeneity of symptoms within each disorder.

  4. [Post-traumatic stress disorder after childbirth].

    PubMed

    Korábová, I; Masopustová, Z

    2016-01-01

    The aim of this paper is to introduce the issue of post-traumatic stress disorder after childbirth to health care professionals. The text focuses on the diagnostic definition of post-traumatic stress disorder after childbirth, symptoms, physiological background, prevalence, course, risk factors and consequences of post-traumatic stress disorder after childbirth for a woman, her child and her partner. Options for interventions and therapy are outlined as well.

  5. Association of Oxidative Stress with Psychiatric Disorders.

    PubMed

    Hassan, Waseem; Noreen, Hamsa; Castro-Gomes, Vitor; Mohammadzai, Imdadullah; da Rocha, Joao Batista Teixeira; Landeira-Fernandez, J

    2016-01-01

    When concentrations of both reactive oxygen species and reactive nitrogen species exceed the antioxidative capability of an organism, the cells undergo oxidative impairment. Impairments in membrane integrity and lipid and protein oxidation, protein mutilation, DNA damage, and neuronal dysfunction are some of the fundamental consequences of oxidative stress. The purpose of this work was to review the associations between oxidative stress and psychological disorders. The search terms were the following: "oxidative stress and affective disorders," "free radicals and neurodegenerative disorders," "oxidative stress and psychological disorders," "oxidative stress, free radicals, and psychiatric disorders," and "association of oxidative stress." These search terms were used in conjunction with each of the diagnostic categories of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders and World Health Organization's International Statistical Classification of Diseases and Related Health Problems. Genetic, pharmacological, biochemical, and preclinical therapeutic studies, case reports, and clinical trials were selected to explore the molecular aspects of psychological disorders that are associated with oxidative stress. We identified a broad spectrum of 83 degenerative syndromes and psychiatric disorders that were associated with oxidative stress. The multi-dimensional information identified herein supports the role of oxidative stress in various psychiatric disorders. We discuss the results from the perspective of developing novel therapeutic interventions.

  6. Post-traumatic stress disorder: advances in psychoneuroimmunology.

    PubMed

    Wong, Cheryl M

    2002-06-01

    Exposure to trauma can result in immune dysregulation, and increasing evidence suggests that there are immune alterations associated with post-traumatic stress disorder (PTSD). However, the exact nature of these immune findings in PTSD has not been defined. The study of psychoneuroimmunology in PTSD is relevant not only for understanding the biological underpinnings of this disorder, but also for establishing the nature of the associations between PTSD and other medical and psychiatric illnesses.

  7. Depressed suicide attempters with posttraumatic stress disorder.

    PubMed

    Ramberg, Maria; Stanley, Barbara; Ystgaard, Mette; Mehlum, Lars

    2015-01-01

    Posttraumatic stress disorder and major depressive disorder are well-established risk factors for suicidal behavior. This study compared depressed suicide attempters with and without comorbid posttraumatic stress disorder with respect to additional diagnoses, global functioning, depressive symptoms, substance abuse, history of traumatic exposure, and suicidal behavior. Adult patients consecutively admitted to a general hospital after a suicide attempt were interviewed and assessed for DSM-IV diagnosis and clinical correlates. Sixty-four patients (71%) were diagnosed with depression; of them, 21 patients (32%) had posttraumatic stress disorder. There were no group differences in social adjustment, depressive symptoms, or suicidal intent. However, the group with comorbid depression and posttraumatic stress disorder had more additional Axis I diagnoses, a higher degree of childhood trauma exposure, and more often reported previous suicide attempts, non-suicidal self-harm, and vengeful suicidal motives. These findings underline the clinical importance of diagnosis and treatment of posttraumatic stress disorder in suicide attempters.

  8. Outcomes of posttraumatic stress disorder.

    PubMed

    Breslau, N

    2001-01-01

    The typical reaction to a life-threatening experience is one of distress, anxiety, and fear. This is characteristic of the basic survival instinct; these emotions enhance the individual's memory of the traumatic experience and thus serve to help in the recognition and avoidance of similarly dangerous situations in the future. In a significant minority of individuals, however, the natural reaction to trauma becomes uncontrollably and disastrously intensified, resulting in the symptoms of posttraumatic stress disorder (PTSD). PTSD varies in severity and duration between individuals, often relating to personal characteristics and the nature of the trauma to which a person is subjected. However, several factors, namely, chronicity, impairment, comorbidity, and somatization, are significantly related to and can influence the course of PTSD and subsequent outcome. This article briefly reviews each of these factors.

  9. Response inhibition and cognitive appraisal in clients with acute stress disorder and posttraumatic stress disorder.

    PubMed

    Abolghasemi, Abass; Bakhshian, Fereshteh; Narimani, Mohammad

    2013-08-01

    The purpose of the present study was to compare response inhibition and cognitive appraisal in clients with acute stress disorder, clients with posttraumatic stress disorder, and normal individuals. This was a comparative study. The sample consisted of 40 clients with acute stress disorder, 40 patients with posttraumatic stress disorder, and 40 normal individuals from Mazandaran province selected through convenience sampling method. Data were collected using Composite International Diagnostic Interview, Stroop Color-Word Test, Posttraumatic Cognitions Inventory, and the Impact of Event Scale. Results showed that individuals with acute stress disorder are less able to inhibit inappropriate responses and have more impaired cognitive appraisals compared to those with posttraumatic stress disorder. Moreover, results showed that response inhibition and cognitive appraisal explain 75% of the variance in posttraumatic stress disorder symptoms and 38% of the variance in posttraumatic stress disorder symptoms. The findings suggest that response inhibition and cognitive appraisal are two variables that influence the severity of posttraumatic stress disorder and acute stress disorder symptoms. Also, these results have important implications for pathology, prevention, and treatment of posttraumatic stress disorder and acute stress disorder.

  10. Molecular Neuroimaging in Posttraumatic Stress Disorder

    PubMed Central

    Im, Jooyeon Jamie; Namgung, Eun; Choi, Yejee; Kim, Jung Yoon; Rhie, Sandy Jeong

    2016-01-01

    Over the past decade, an increasing number of neuroimaging studies have provided insight into the neurobiological mechanisms of posttraumatic stress disorder (PSTD). In particular, molecular neuroimaging techniques have been employed in examining metabolic and neurochemical processes in PTSD. This article reviews molecular neuroimaging studies in PTSD and focuses on findings using three imaging modalities including positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetic resonance spectroscopy (MRS). Although there were some inconsistences in the findings, patients with PTSD showed altered cerebral metabolism and perfusion, receptor bindings, and metabolite profiles in the limbic regions, medial prefrontal cortex, and temporal cortex. Studies that have investigated brain correlates of treatment response are also reviewed. Lastly, the limitations of the molecular neuroimaging studies and potential future research directions are discussed. PMID:28035179

  11. Posttraumatic Stress Disorder and Substance Use Disorders in College Students

    ERIC Educational Resources Information Center

    Borsari, Brian; Read, Jennifer P.; Campbell, James F.

    2008-01-01

    Research indicates that many college students report posttraumatic stress disorder (PTSD) or substance use disorder (SUD), yet there has been scant attention paid to the co-occurrence of these disorders in college students. This review examines the co-occurrence of PTSD and SUD in college students. Recommendations for counseling centers are…

  12. Neonatal handling alters maternal emotional response to stress.

    PubMed

    Reis, Adolfo R; Jacobs, Silvana; Menegotto, Pâmela R; Silveira, Patrícia P; Lucion, Aldo B

    2016-07-01

    Neonatal handling is an experimental procedure used to analyze the effects of environmental interventions during early postpartum days (PPD). Long-lasting effects of repeated stress exposure in the neonatal period on the maternal side are poorly studied in this model. The aim of this study was to verify if handling the pups induces enduring effects on damśstress responses, increasing their risk for depression. Dams were divided into two groups (NH-Non-handled and H-Handled) based on the handling procedure (pups were handled for 1 min/per day from PPD1-PPD10) and then subdivided into four groups (NH, NH + S, H, and H + S) based on the exposure or not to restraint stress after weaning (1 hr/per day for 7 days, PPD22-PPD28). We analyzed damśbehavior in the forced swimming test (FST PPD29-PPD30), plasma basal corticosterone and BDNF levels, as well as adrenal weight (PPD31). The results show that handling alters the stress response of dams to acute and chronic stress, as evidenced by dams of the H group having increased immobility in the first day of FST (p < .001), similar to NH + S (p < .01). Dams of the H and H + S groups show decreased levels of corticosterone when compared to NH and NH + S groups (p < .05), but the H + S group shows an increased adrenal weight, suggesting an increased sensibility of the maternal organism to the chronic stress applied after weaning (p < .05). We show that handling may induce a long-lasting effect on maternal stress response; these changes in the damśemotional reactivity increase their susceptibility for the development of psychiatric disorders such as depression. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 58: 614-622, 2016. © 2016 Wiley Periodicals, Inc.

  13. Post-Traumatic Stress Disorder - Multiple Languages

    MedlinePlus

    ... Are Here: Home → Multiple Languages → All Health Topics → Post-Traumatic Stress Disorder URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Post-Traumatic Stress Disorder - Multiple Languages To use the sharing features on ...

  14. Post-traumatic Stress Disorder.

    PubMed

    Javidi, H; Yadollahie, M

    2012-01-01

    Unexpected extreme sudden traumatic stressor may cause post-traumatic stress disorder (PTSD). Important traumatic events include war, violent personal assault (e.g., sexual assault, and physical attack), being taken hostage or kidnapped, confinement as a prisoner of war, torture, terrorist attack, severe car accidents, and natural disasters. In childhood age sexual abuse or witnessing serious injuries or unexpected death of a beloved one are among important traumatic events.PTSD can be categorized into two types of acute and chronic PTSD: if symptoms persist for less than three months, it is termed "acute PTSD," otherwise, it is called "chronic PTSD." 60.7% of men and 51.2% of women would experience at least one potentially traumatic event in their lifetime. The lifetime prevalence of PTSD is significantly higher in women than men. Lifetime prevalence of PTSD varies from 0.3% in China to 6.1% in New Zealand. The prevalence of PTSD in crime victims are between 19% and 75%; rates as high as 80% have been reported following rape. The prevalence of PTSD among direct victims of disasters was reported to be 30%-40%; the rate in rescue workers was 10%-20%. The prevalence of PTSD among police, fire, and emergency service workers ranged from 6%-32%. An overall prevalence rate of 4% for the general population, the rate in rescue/recovery occupations ranged from 5% to 32%, with the highest rate reported in search and rescue personnel (25%), firefighters (21%), and workers with no prior training for facing disaster. War is one of the most intense stressors known to man. Armed forces have a higher prevalence of depression, anxiety disorders, alcohol abuse and PTSD. High-risk children who have been abused or experienced natural disasters may have an even higher prevalence of PTSD than adults.Female gender, previous psychiatric problem, intensity and nature of exposure to the traumatic event, and lack of social support are known risk factors for work-related PTSD. Working with

  15. Dissociation and Alterations in Brain Function and Structure: Implications for Borderline Personality Disorder.

    PubMed

    Krause-Utz, Annegret; Frost, Rachel; Winter, Dorina; Elzinga, Bernet M

    2017-01-01

    Dissociation involves disruptions of usually integrated functions of consciousness, perception, memory, identity, and affect (e.g., depersonalization, derealization, numbing, amnesia, and analgesia). While the precise neurobiological underpinnings of dissociation remain elusive, neuroimaging studies in disorders, characterized by high dissociation (e.g., depersonalization/derealization disorder (DDD), dissociative identity disorder (DID), dissociative subtype of posttraumatic stress disorder (D-PTSD)), have provided valuable insight into brain alterations possibly underlying dissociation. Neuroimaging studies in borderline personality disorder (BPD), investigating links between altered brain function/structure and dissociation, are still relatively rare. In this article, we provide an overview of neurobiological models of dissociation, primarily based on research in DDD, DID, and D-PTSD. Based on this background, we review recent neuroimaging studies on associations between dissociation and altered brain function and structure in BPD. These studies are discussed in the context of earlier findings regarding methodological differences and limitations and concerning possible implications for future research and the clinical setting.

  16. [Stress, mental disorders and coronary heart disease].

    PubMed

    Lederbogen, F; Ströhle, A

    2012-11-01

    There are numerous associations between stress, mental disorders and coronary heart disease (CHD). Exposure to an acute stressor leads to activation of the hypothalamus-pituitary-adrenal and sympathoadrenal systems and chronic stressors are associated with sustained functional changes of these systems. Experiencing acute and chronic stress is paralleled by an increased incidence of mental disorders with the most consistent evidence on the triggering of major depressive episodes. Various mental disorders, including depression, anxiety and schizophrenia, are associated with an increased risk of CHD. Furthermore, acute and chronic stressors have been identified as risk factors or triggers of acute coronary syndromes. Thus therapeutic strategies aim at reducing subjective stress experience, therapy of mental disorders and treatment of cardiac risk factors known to be more prevalent in increased stress states and mental disorders.

  17. Pharmacotherapy for posttraumatic stress disorder.

    PubMed

    Stein, D J; Zungu-Dirwayi, N; van Der Linden GJ; Seedat, S

    2000-01-01

    Posttraumatic stress disorder (PTSD) is a prevalent and disabling disorder. By definition prior psychological trauma plays a causal role in the disorder, and psychotherapy is a widely accepted intervention. Nevertheless there is growing evidence that PTSD is characterized by specific psychobiological dysfunctions, and this has contributed to a growing interest in the use of medication in its treatment. The authors aimed to undertake a systematic review of randomized controlled trials (RCTs) of the pharmacotherapy of posttraumatic stress disorder (PTSD) following the guidelines and using the software of the Cochrane Collaboration, and to provide an estimate of the effects of medication in this disorder. Secondary objectives were to explore questions about whether particular classes of medication are more effective and/or acceptable than others in the treatment of PTSD, and about which factors (clinical and methodological) predict response to pharmacotherapy. Studies of the pharmacotherapy of PTSD were identified using literature searches of MEDLINE (1966 to 1999, using the textwords posttraumatic, post-traumatic, medication, pharmacotherapy) and other electronic databases (PSYCLIT; National PTSD Center Pilots database; Dissertation Abstracts; Cochrane Collaboration Depression, Anxiety & Neurosis Controlled Trials Register). In addition, published and unpublished RCTs were requested from PTSD researchers and pharmaceutical companies. An initial broad strategy was undertaken to find not only RCTs, but also open-label trials and reviews of the pharmacotherapy of PTSD; additional studies were sought in reference lists of retrieved articles and included studies in any language. All RCTs of PTSD (including both placebo controlled and comparative trials), whether published or unpublished, but completed prior to the end of 1999 were considered for the review. Selected RCTs were independently assessed and collated by 2 raters, and Review Manager (RevMan) software was used to

  18. Oxidative stress and metabolic disorders: Pathogenesis and therapeutic strategies.

    PubMed

    Rani, Vibha; Deep, Gagan; Singh, Rakesh K; Palle, Komaraiah; Yadav, Umesh C S

    2016-03-01

    Increased body weight and metabolic disorder including insulin resistance, type 2 diabetes and cardiovascular complications together constitute metabolic syndrome. The pathogenesis of metabolic syndrome involves multitude of factors. A number of studies however indicate, with some conformity, that oxidative stress along with chronic inflammatory condition pave the way for the development of metabolic diseases. Oxidative stress, a state of lost balance between the oxidative and anti-oxidative systems of the cells and tissues, results in the over production of oxidative free radicals and reactive oxygen species (ROS). Excessive ROS generated could attack the cellular proteins, lipids and nucleic acids leading to cellular dysfunction including loss of energy metabolism, altered cell signalling and cell cycle control, genetic mutations, altered cellular transport mechanisms and overall decreased biological activity, immune activation and inflammation. In addition, nutritional stress such as that caused by high fat high carbohydrate diet also promotes oxidative stress as evident by increased lipid peroxidation products, protein carbonylation, and decreased antioxidant system and reduced glutathione (GSH) levels. These changes lead to initiation of pathogenic milieu and development of several chronic diseases. Studies suggest that in obese person oxidative stress and chronic inflammation are the important underlying factors that lead to development of pathologies such as carcinogenesis, obesity, diabetes, and cardiovascular diseases through altered cellular and nuclear mechanisms, including impaired DNA damage repair and cell cycle regulation. Here we discuss the aspects of metabolic disorders-induced oxidative stress in major pathological conditions and strategies for their prevention and therapy.

  19. Posttraumatic Stress Disorder and Psychopathology in Dancers.

    PubMed

    Thomson, Paula; Jaque, S Victoria

    2015-09-01

    This study investigated the prevalence of posttraumatic stress disorder (PTSD) in pre-professional and professional dancers (n=209) who were exposed to traumatic events. Nine self-report instruments assessed (1) adverse childhood experiences, (2) past traumatic events, (3) coping strategies under stressful situations, and (4) fantasy proneness. The psychopathology variables included (5) anxiety, (6) depression, (7) dissociation, (8) shame, and (9)) PTSD diagnostic scale. Statistical calculations included descriptive, distributional, and multivariate analysis of covariates (MANCOVA). Results indicate that dancers had a significantly higher distribution of PTSD (20.2%) compared to the normal population (7.8%). They also had a higher frequency of family members with mental illness, an inability to speak about their trauma, and more suicidal thoughts. The PTSD group of dancers had higher levels of psychopathology (anxiety, depression, dissociation, and shame) and they had more childhood adversity and adult trauma. Compared to the no-PTSD group, the PTSD group had higher scores on fantasy proneness and emotion-oriented coping strategies. These coping strategies may increase psychological instability. Addressing early abuse and trauma is recommended. Clinicians may help dancers alter their internal working models that their self is worthless, others are abusive, and the world is threatening and dangerous. By understanding PTSD in dancers, medical and mental health treatment protocols may be established to address the debilitating, and often hidden, symptoms of PTSD.

  20. Salivary Cortisol Lower in Posttraumatic Stress Disorder

    PubMed Central

    Wahbeh, Helané; Oken, Barry S.

    2013-01-01

    Altered cortisol has been demonstrated to be lower in posttraumatic stress disorder (PTSD) in most studies. This cross-sectional study evaluated salivary cortisol at waking, 30 minutes after, and bedtime in 51 combat veterans with PTSD compared to 20 veterans without PTSD. It also examined the relationship of cortisol to PTSD symptoms using two classifications: DSM-IV and the more recent four-factor classification proposed for DSM-V. The PTSD group had lower cortisol values than the control group (F(6, 69) = 3.35, p = .006). This significance did not change when adding age, body mass index, smoking, medications affecting cortisol, awakening time, sleep duration, season, depression, perceived stress, service era, combat exposure, and lifetime trauma as covariates. Post-hoc analyses revealed that the PTSD group had lower area under the curve ground and waking, 30min, and bedtime values while the cortisol awakening response and area under the curve increase were not different between groups. The four-factor avoidance PTSD symptom cluster was associated with cortisol but not the other symptom clusters. This study supports the finding that cortisol is lower in people with PTSD. PMID:23529862

  1. Altered brain reward circuits in eating disorders: chicken or egg?

    PubMed

    Frank, Guido K W

    2013-10-01

    The eating disorders anorexia nervosa (AN) and bulimia nervosa (BN) are severe psychiatric disorders with high mortality. Our knowledge about the neurobiology of eating disorders is very limited, and the question remains whether alterations in brain structure or function in eating disorders are state related, remnants of the illness or premorbid traits. The brain reward system is a relatively well-characterized brain circuitry that plays a central role in the drive to eat and individuals with current or past eating disorders showed alterations in those pathways compared to controls. Here we propose that structural and functional alterations in the insula and frontal cortex, including orbitofrontal and cingulate regions, areas that contribute to reward and anxiety processing, could predispose to developing an eating disorder and that adaptive changes in those circuits in response to malnutrition or repeated binge eating and purging could further promote illness behavior, hinder recovery and contribute to relapse.

  2. Posttraumatic stress disorders in children and adolescents.

    PubMed

    Perry, B D; Azad, I

    1999-08-01

    Millions of children are exposed to traumatic experiences each year. Over 30% of these children develop a clinical syndrome with emotional, behavioral, cognitive, social, and physical symptoms called posttraumatic stress disorder. The symptoms of posttraumatic stress disorder fall into three clusters: reenactment of the traumatic event: avoidance of cues associated with the event or general withdrawal; and physiological hyperreactivity. Significant physical and medical problems in childhood, adolescence, and adulthood appear to be related to childhood trauma. Current treatment approaches include postacute psychoeducation, individual psychotherapy, pharmacotherapy, and cognitive-behavioral therapy. Despite increasing attention over the past 10 years, childhood posttraumatic stress disorder remains an understudied public health problem.

  3. Germ Cell Origins of Posttraumatic Stress Disorder Risk: The Transgenerational Impact of Parental Stress Experience.

    PubMed

    Rodgers, Ali B; Bale, Tracy L

    2015-09-01

    Altered stress reactivity is a predominant feature of posttraumatic stress disorder (PTSD) and may reflect disease vulnerability, increasing the probability that an individual will develop PTSD following trauma exposure. Environmental factors, particularly prior stress history, contribute to the developmental programming of the hypothalamic-pituitary-adrenal stress axis. Critically, the consequences of stress experiences are transgenerational, with parental stress exposure impacting stress reactivity and PTSD risk in subsequent generations. Potential molecular mechanisms underlying this transmission have been explored in rodent models that specifically examine the paternal lineage, identifying epigenetic signatures in male germ cells as possible substrates of transgenerational programming. Here, we review the role of these germ cell epigenetic marks, including posttranslational histone modifications, DNA methylation, and populations of small noncoding RNAs, in the development of offspring stress axis sensitivity and disease risk.

  4. Normal Stress or Adjustment Disorder?

    MedlinePlus

    ... and stressor-related disorders. In: Diagnostic and Statistical Manual of Mental Disorders DSM-5. 5th ed. Arlington, Va.: American Psychiatric Association; 2013. http://www.psychiatryonline.org. Accessed Dec. 1, ...

  5. Stress sensitivity and the development of affective disorders.

    PubMed

    Bale, Tracy L

    2006-11-01

    Depressive disorders are the most common form of mental illness in America, affecting females twice as often as males. The great variability of symptoms and responses to therapeutic treatment emphasize the complex underlying neurobiology of disease onset and progression. Evidence from human and animal studies reveals a vital link between individual stress sensitivity and the predisposition toward mood disorders. While the stress response is essential for maintenance of homeostasis and survival, chronic stress and maladaptive responses to stress insults can lead to depression or other affective disorders. A key factor in the mediation of stress responsivity is the neuropeptide corticotropin-releasing factor (CRF). Studies in animal models of heightened stress sensitivity have illustrated the involvement of CRF downstream neurotransmitter targets, including serotonin and norepinephrine, in the profound neurocircuitry failure that may underlie maladaptive coping strategies. Stress sensitivity may also be a risk factor in affective disorder development susceptibility. As females show an increased stress response and recovery time compared to males, they may be at an increased vulnerability for disease. Therefore, examination of sex differences in CRF and downstream targets may aid in the elucidation of the underlying causes of the increased disease presentation in females. While we continue to make progress in our understanding of mood disorder etiology, we still have miles to go before we sleep. As an encouraging number of new animal models of altered stress sensitivity and negative stress coping strategies have been developed, the future looks extremely promising for the possibility of a new generation of drug targets to be developed.

  6. Stress and disorders of the stress system.

    PubMed

    Chrousos, George P

    2009-07-01

    All organisms must maintain a complex dynamic equilibrium, or homeostasis, which is constantly challenged by internal or external adverse forces termed stressors. Stress occurs when homeostasis is threatened or perceived to be so; homeostasis is re-established by various physiological and behavioral adaptive responses. Neuroendocrine hormones have major roles in the regulation of both basal homeostasis and responses to threats, and are involved in the pathogenesis of diseases characterized by dyshomeostasis or cacostasis. The stress response is mediated by the stress system, partly located in the central nervous system and partly in peripheral organs. The central, greatly interconnected effectors of this system include the hypothalamic hormones arginine vasopressin, corticotropin-releasing hormone and pro-opiomelanocortin-derived peptides, and the locus ceruleus and autonomic norepinephrine centers in the brainstem. Targets of these effectors include the executive and/or cognitive, reward and fear systems, the wake-sleep centers of the brain, the growth, reproductive and thyroid hormone axes, and the gastrointestinal, cardiorespiratory, metabolic, and immune systems. Optimal basal activity and responsiveness of the stress system is essential for a sense of well-being, successful performance of tasks, and appropriate social interactions. By contrast, excessive or inadequate basal activity and responsiveness of this system might impair development, growth and body composition, and lead to a host of behavioral and somatic pathological conditions.

  7. Treating Comorbid Panic Disorder in Veterans With Posttraumatic Stress Disorder

    ERIC Educational Resources Information Center

    Teng, Ellen J.; Bailey, Sara D.; Chaison, Angelic D.; Petersen, Nancy J.; Hamilton, Joseph D.; Dunn, Nancy Jo

    2008-01-01

    This study compares the effectiveness of panic control treatment (PCT) with that of a psychoeducational supportive treatment (PE-SUP) in treating panic disorder among a veteran sample with a primary diagnosis of chronic posttraumatic stress disorder (PTSD). Thirty-five patients randomized to receive 10 individual sessions of either PCT or PE-SUP…

  8. Borderline Personality Disorder and Posttraumatic Stress Disorder: Time for Integration?

    ERIC Educational Resources Information Center

    Hodges, Shannon

    2003-01-01

    An increasing prevalence of borderline personality disorder (BPD) and posttraumatic stress disorder (PTSD) diagnoses among women illustrates problems and limitations of the medical model system. Article explores overlapping relationship between BPD and PTSD and critiques how both are viewed within the mental health community. Previous research is…

  9. Integrating Treatment of Posttraumatic Stress Disorder and Substance Use Disorder

    ERIC Educational Resources Information Center

    Ford, Julian D.; Russo, Eileen M.; Mallon, Sharon D.

    2007-01-01

    Historically, administrators and clinicians have been hesitant to address posttraumatic stress disorder (PTSD) in the treatment of substance use disorders (SUDs). However, research shows that SUD treatment recruitment and outcomes may be adversely affected if co-occurring PTSD is left untreated. The authors provide guidelines for screening and…

  10. Borderline Personality Disorder and Posttraumatic Stress Disorder: Time for Integration?

    ERIC Educational Resources Information Center

    Hodges, Shannon

    2003-01-01

    An increasing prevalence of borderline personality disorder (BPD) and posttraumatic stress disorder (PTSD) diagnoses among women illustrates problems and limitations of the medical model system. Article explores overlapping relationship between BPD and PTSD and critiques how both are viewed within the mental health community. Previous research is…

  11. Pheochromocytoma: an endocrine stress mimicking disorder.

    PubMed

    Kantorovich, Vitaly; Eisenhofer, Graeme; Pacak, Karel

    2008-12-01

    A pheochromocytoma is an endocrine tumor that can uniquely mimic numerous stress-associated disorders, with variations in clinical manifestations resulting from different patterns of catecholamine secretion and actions of released catecholamines on physiological systems.

  12. PHEOCHROMOCYTOMA: AN ENDOCRINE STRESS MIMICKING DISORDER

    PubMed Central

    Kantorovich, Vitaly; Eisenhofer, Graeme; Pacak, Karel

    2008-01-01

    Pheochromocytoma is an endocrine tumor that can uniquely mimic numerous stress-associated disorders, with variations in clinical manifestations resulting from different patterns of catecholamine secretion and actions of released catecholamines on physiological systems. PMID:19120142

  13. Postmodern Stress Disorder (PMSD): A Possible New Disorder.

    PubMed

    Eiser, Arnold R

    2015-11-01

    The murder of cardiovascular surgeon, Michael Davidson, MD, suggests the existence of a new disorder, postmodern stress disorder. This disorder is characterized by repetitive exposure to digital images of violence in a variety of electronic media, including films, television, video games, music videos, and other online sources. This disorder appears to be a variant of posttraumatic stress disorder, and shares with it excessive stimulation of the amygdala and loss of the normal inhibitory inputs from the orbitofrontal cingulate cortical gyrus. In postmodern stress disorder, repetitive digital microtraumas appear to have an effect similar to that of macrotraumas of warfare or civilian assaults. Other elements of the disorder include the development of fixed ideas of bullying or public shaming, access to weapons, and loss of impulse control. This syndrome could explain a number of previously inexplicable murders/suicides. Violence against health care professionals is a profound concern for the medical profession, as are assaults on nonclinicians. The recommendation is made to change forensic procedures to include obtaining historic information concerning the use of digital media during investigations of violent crimes and murders so that the disorder may be further characterized. Gaining an understanding of this disorder will require a multidisciplinary approach to this life-threatening public health problem. Research should also focus on the development and evaluation of possible antidotes to postmodern toxicities.

  14. Neurochemical alterations associated with borderline personality disorder.

    PubMed

    Atmaca, Murad; Karakoc, Tevfik; Mermi, Osman; Gurkan Gurok, M; Yildirim, Hanefi

    2015-01-01

    In neuroimaging on borderline personality disorder, prior studies focused on the hippocampus and amygdala, as mentioned above. However, no study investigated whether there were neurochemical changes in the patients with borderline personality disorder. Therefore, in the present study, we aimed to investigate neurochemical change of patients diagnosed with borderline disorder and hypothesized that neurochemicals would change in the hippocampus region of these patients. Seventeen patients and the same number of healthy control subjects were analyzed by using a 1.5 Tesla GE Signa Imaging System. N-acetylaspartate (NAA), choline compounds (CHO), and creatine (CRE) values of hippocampal region were measured. The mean NAA/CRE ratio in the hippocampus region was significantly reduced in the patients with borderline personality disorder compared to that of healthy control subjects, In addition, NAA/CHO ratio of the patients with borderline personality disorder was also significantly reduced when compared to that of healthy subjects. There was no difference in the ratio of CHO/CRE. In summary, we present evidence for reduced NAA in the patients with borderline personality disorder.

  15. [Post traumatic stress disorder among assault victims].

    PubMed

    Carbonell, Carmen Gloria; Carvajal, César

    2004-07-01

    Urban violence is increasing in Metropolitan Santiago and assault victims may suffer from post traumatic stress disorders. To study the clinical and evolutive profile of post traumatic stress disorders among assault victims. Retrospective review of medical records of assault victims with post traumatic stress disorder, that were attended at the Hospital del Trabajador between 1987 and 2000. The features of these patients were compared with other patients with post traumatic stress disorders not caused by assaults. The records of 140 subjects (88 female) aged 34.9+/-10.9 years old, were reviewed. Seventy one percent of subjects worked as clerks and 59% were attended during the first month after the assault. Treatment with psychotherapy and psychotropic drugs lasted a median of 60 days and 62% was discharged before completing three months of treatment. These subjects used more antidepressants and had more physical lesions than subjects with a post traumatic stress disorder not caused by assaults. Timely diagnosis and treatment of post traumatic stress disorders caused by assaults, results in a favorable outcome in two thirds of patients.

  16. An altered peripheral IL6 response in major depressive disorder

    PubMed Central

    Money, Kelli M.; Olah, Zita; Korade, Zeljka; Garbett, Krassimira A.; Shelton, Richard C.; Mirnics, Karoly

    2016-01-01

    Major depressive disorder (MDD) is one of the most prevalent major psychiatric disorders with a lifetime prevalence of 17%. Recent evidence suggests MDD is not only a brain dysfunction, but a systemic disease affecting the whole body. Central and peripheral inflammatory changes seem to be a centerpiece of MDD pathology: a subset of patients show elevated blood cytokine and chemokine levels that partially normalize with symptom improvement over the course of antidepressant treatment. As this inflammatory process in MDD is poorly understood, we hypothesized that the peripheral tissues of MDD patients will respond differently to inflammatory stimuli, resulting in an aberrant transcriptional response to elevated proinflammatory cytokines. To test this, we used MDD patient- and control-derived dermal fibroblast cultures to investigate their response to an acute treatment with IL6, IL1β, TNFα, or vehicle. Following RNA isolation and subsequent cDNA synthesis, quantitative PCR was used to determine the relative expression level of several families of inflammation-responsive genes. Our results showed comparable expression of the tested genes between MDD patients and controls at baseline. In contrast, MDD patient fibroblasts had a diminished transcriptional response to IL6 in all the gene sets tested (oxidative stress response, mitochondrial function, and lipid metabolism). We also found a significant increase in baseline and IL6 stimulated transcript levels of the IL6 receptor gene. This IL6 receptor transcript increase in MDD fibroblasts was accompanied by an IL6 stimulated increase in induction of SOCS3, which dampens IL6 receptor signaling. Altogether our results demonstrate that there is an altered transcriptional response to IL6 in MDD, which may represent one of the molecular mechanisms contributing to disease pathophysiology. Ultimately we hope that these studies will lead to validation of novel MDD drug targets focused on normalizing the altered IL6 response in

  17. An altered peripheral IL6 response in major depressive disorder.

    PubMed

    Money, Kelli M; Olah, Zita; Korade, Zeljka; Garbett, Krassimira A; Shelton, Richard C; Mirnics, Karoly

    2016-05-01

    Major depressive disorder (MDD) is one of the most prevalent major psychiatric disorders with a lifetime prevalence of 17%. Recent evidence suggests MDD is not only a brain dysfunction, but a systemic disease affecting the whole body. Central and peripheral inflammatory changes seem to be a centerpiece of MDD pathology: a subset of patients show elevated blood cytokine and chemokine levels that partially normalize with symptom improvement over the course of anti-depressant treatment. As this inflammatory process in MDD is poorly understood, we hypothesized that the peripheral tissues of MDD patients will respond differently to inflammatory stimuli, resulting in an aberrant transcriptional response to elevated pro-inflammatory cytokines. To test this, we used MDD patient- and control-derived dermal fibroblast cultures to investigate their response to an acute treatment with IL6, IL1β, TNFα, or vehicle. Following RNA isolation and subsequent cDNA synthesis, quantitative PCR was used to determine the relative expression level of several families of inflammation-responsive genes. Our results showed comparable expression of the tested genes between MDD patients and controls at baseline. In contrast, MDD patient fibroblasts had a diminished transcriptional response to IL6 in all the gene sets tested (oxidative stress response, mitochondrial function, and lipid metabolism). We also found a significant increase in baseline and IL6 stimulated transcript levels of the IL6 receptor gene. This IL6 receptor transcript increase in MDD fibroblasts was accompanied by an IL6 stimulated increase in induction of SOCS3, which dampens IL6 receptor signaling. Altogether our results demonstrate that there is an altered transcriptional response to IL6 in MDD, which may represent one of the molecular mechanisms contributing to disease pathophysiology. Ultimately we hope that these studies will lead to validation of novel MDD drug targets focused on normalizing the altered IL6 response in

  18. Psychiatric Comorbidity in Childhood Post Traumatic Stress Disorder.

    ERIC Educational Resources Information Center

    Famularo, Richard; And Others

    1996-01-01

    This study of 117 severely abused children found that 35% exhibited evidence of posttraumatic stress disorder (PTSD). Results indicated that PTSD was correlated with attention deficit disorders, anxiety disorders, psychotic disorders, suicidal ideation, and mood disorders. (CR)

  19. Gender Differences in Posttraumatic Stress Disorder

    ERIC Educational Resources Information Center

    Olff, Miranda; Langeland, Willie; Draijer, Nel; Gersons, Berthold P. R.

    2007-01-01

    One of the most consistent findings in the epidemiology of posttraumatic stress disorder (PTSD) is the higher risk of this disorder in women. Explanations reviewed within a psychobiological model of PTSD suggest that women's higher PTSD risk may be due to the type of trauma they experience, their younger age at the time of trauma exposure, their…

  20. Brief Psychotherapy for Posttraumatic Stress Disorders.

    ERIC Educational Resources Information Center

    Brom, Daniel; And Others

    1989-01-01

    Examined the effectiveness of psychotherapeutic methods for the treatment of posttraumatic stress disorders. Compared trauma desensitization, hypnotherapy, psychodynamic therapy and control condition for 112 persons suffering from serious disorders resulting from traumatic events in the past 5 years. Results indicated that treated cases were…

  1. Imagery Rescripting in Posttraumatic Stress Disorder

    ERIC Educational Resources Information Center

    Hackmann, Anne

    2011-01-01

    This article provides an overview of methods of working with imagery to change meanings and ameliorate posttraumatic stress disorder (PTSD). It opens with a description of phenomenology in this disorder, usually characterized by a small number of recurrent images of the trauma, each representing a moment that warned of a threat to the physical or…

  2. Adolescent Post-Traumatic Stress Disorder

    ERIC Educational Resources Information Center

    Yule, William

    2003-01-01

    Based on over a decade of work in the area of PTSD, including a longitudinal study of PTSD among adolescents, Dr. Yule provides an introduction to post-traumatic stress disorder as it occurs in youth. This includes a look at the manifestations of stress reactions, the incidence and prevalence of PTSD, and the relationship between levels of…

  3. Adolescent Post-Traumatic Stress Disorder

    ERIC Educational Resources Information Center

    Yule, William

    2003-01-01

    Based on over a decade of work in the area of PTSD, including a longitudinal study of PTSD among adolescents, Dr. Yule provides an introduction to post-traumatic stress disorder as it occurs in youth. This includes a look at the manifestations of stress reactions, the incidence and prevalence of PTSD, and the relationship between levels of…

  4. Endoplasmic Reticulum (ER) Stress and Endocrine Disorders.

    PubMed

    Ariyasu, Daisuke; Yoshida, Hiderou; Hasegawa, Yukihiro

    2017-02-11

    The endoplasmic reticulum (ER) is the organelle where secretory and membrane proteins are synthesized and folded. Unfolded proteins that are retained within the ER can cause ER stress. Eukaryotic cells have a defense system called the "unfolded protein response" (UPR), which protects cells from ER stress. Cells undergo apoptosis when ER stress exceeds the capacity of the UPR, which has been revealed to cause human diseases. Although neurodegenerative diseases are well-known ER stress-related diseases, it has been discovered that endocrine diseases are also related to ER stress. In this review, we focus on ER stress-related human endocrine disorders. In addition to diabetes mellitus, which is well characterized, several relatively rare genetic disorders such as familial neurohypophyseal diabetes insipidus (FNDI), Wolfram syndrome, and isolated growth hormone deficiency type II (IGHD2) are discussed in this article.

  5. Endoplasmic Reticulum (ER) Stress and Endocrine Disorders

    PubMed Central

    Ariyasu, Daisuke; Yoshida, Hiderou; Hasegawa, Yukihiro

    2017-01-01

    The endoplasmic reticulum (ER) is the organelle where secretory and membrane proteins are synthesized and folded. Unfolded proteins that are retained within the ER can cause ER stress. Eukaryotic cells have a defense system called the “unfolded protein response” (UPR), which protects cells from ER stress. Cells undergo apoptosis when ER stress exceeds the capacity of the UPR, which has been revealed to cause human diseases. Although neurodegenerative diseases are well-known ER stress-related diseases, it has been discovered that endocrine diseases are also related to ER stress. In this review, we focus on ER stress-related human endocrine disorders. In addition to diabetes mellitus, which is well characterized, several relatively rare genetic disorders such as familial neurohypophyseal diabetes insipidus (FNDI), Wolfram syndrome, and isolated growth hormone deficiency type II (IGHD2) are discussed in this article. PMID:28208663

  6. Cortisol stress reactivity across psychiatric disorders: A systematic review and meta-analysis.

    PubMed

    Zorn, Jelle V; Schür, Remmelt R; Boks, Marco P; Kahn, René S; Joëls, Marian; Vinkers, Christiaan H

    2017-03-01

    The hypothalamus-pituitary-adrenal (HPA) axis and its end product cortisol are essential for an adequate response to stress. Considering the role of stress as a risk factor for psychiatric disorders, it is not surprising that cortisol stress reactivity has frequently been investigated in patients versus healthy individuals. However, the large heterogeneity in measures of the cortisol stress response has hampered a systematic evaluation of the evidence. We here report of a systematic literature review and meta-analysis on cortisol reactivity to psychosocial stress across psychiatric disorders. Original data from authors were obtained to construct standardized cortisol outcomes (the areas under the curve with respect to increase (AUCi) and ground (AUCg)) and to examine the influence of sex and symptomatic state on cortisol stress reactivity. Fourteen studies on major depressive disorder (MDD) (n=1129), 9 on anxiety disorders (n=732, including social anxiety disorder (SAD), posttraumatic stress disorder, panic disorder and mixed samples of anxiety disorders) and 4 on schizophrenia (n=180) were included that used the Trier Social Stress Test or an equivalent psychosocial stress task. Sex-dependent changes in stress reactivity were apparent in MDD and anxiety disorders. Specifically, women with current MDD or an anxiety disorder exhibited a blunted cortisol stress response, whereas men with current MDD or SAD showed an increased cortisol response to psychosocial stress. In individuals with remitted MDD, altered cortisol stress reactivity was less pronounced in women and absent in men. For schizophrenia, cortisol stress reactivity was blunted in both men and women, but the number of studies was limited and showed evidence for publication bias. These findings illustrate that sharing individual data to disentangle the effects of sex, symptom levels and other factors is essential for further understanding of the alterations in cortisol stress reactivity across psychiatric

  7. Paediatric stress: from neuroendocrinology to contemporary disorders.

    PubMed

    Stavrou, Stavroula; Nicolaides, Nicolas C; Critselis, Elena; Darviri, Christina; Charmandari, Evangelia; Chrousos, George P

    2017-03-01

    Stress is defined as a state of threatened or perceived as threatened homeostasis. A broad spectrum of extrinsic or intrinsic, real or perceived stressful stimuli, called 'stressors', activates a highly conserved system, the 'stress system', which adjusts homeostasis through central and peripheral neuroendocrine responses. Inadequate, excessive or prolonged adaptive responses to stress may underlie the pathogenesis of several disease states prevalent in modern societies. The development and severity of these conditions primarily depend on the genetic vulnerability of the individual, the exposure to adverse environmental factors and the timing of the stressful event(s), given that prenatal life, infancy, childhood and adolescence are critical periods characterized by increased vulnerability to stressors. We conducted a systematic review of original articles and reviews published in MEDLINE from 1975 through June 2016. The search terms were 'childhood stress', 'pediatric stress', 'stress and disorders' and 'stress management'. In this review, we discuss the historical and neuroendocrine aspects of stress, and we present representative examples of paediatric stress system disorders, such as early-life adversity, obesity and bullying. We also discuss the adverse impact of a socio-economic crisis on childhood health. The tremendous progress of epigenetics has enabled us to have a deeper understanding of the molecular mechanisms underlying paediatric stress-related disorders. The need for early successful stress management techniques to decrease the incidence of paediatric stress-related diseases, as well as to prevent the development of several pathologic conditions in adolescence and adulthood, is imperative. © 2017 Stichting European Society for Clinical Investigation Journal Foundation.

  8. Stresses on the cervical column associated with vertical occlusal alteration.

    PubMed

    Motoyoshi, Mitsuru; Shimazaki, Takahisa; Hosoi, Kohei; Wada, Mizuki; Namura, Shinkichi

    2003-04-01

    The biomechanical effects on cervical vertebral columns (C1-C7) during mastication were calculated using a three-dimensional (3D) finite element method. To verify the biomechanical influences of vertical occlusal alteration to the cervical column, three finite element models (FEM) showing a normal (model A), a steep (model B), and a flat occlusal plane (model C) were constructed. The occlusal stress distribution showed various patterns for the three models; the stress extended to the anterior area as the occlusal plane became steeper. The plots of the stresses on the mid sagittal section of the cervical columns showed different patterns for the three models; the stress converged at the odontoid process in models A and B, whereas the stresses at C7 in model B tended to decrease compared with model A. Concentrated stress was observed at C5 in model C, supporting the hypothesis that vertical occlusal alteration could influence stress distribution in the cervical columns.

  9. The psychobiology of posttraumatic stress disorder.

    PubMed

    van der Kolk, B A

    1997-01-01

    This review summarizes the current state of our knowledge of the psychobiology of posttraumatic stress disorder (PTSD). People with PTSD develop an enduring vigilance for and sensitivity to environmental threat. They have difficulty in properly evaluating sensory stimuli and responding with appropriate levels of physiologic and neurohormonal arousal. The inappropriate mobilization of biological emergency responses to innocuous stimuli is mirrored psychologically in an inability to properly integrate memories of the trauma and in a fixation on the past. The biological dysregulation of PTSD can be measured on physiologic, neurohormonal, immunologic, and functional neuroanatomical levels. The developmental level at which the trauma occurs affects the nature and extent of psychobiological disruptions. The availability of neuroimaging for documenting structural and functional abnormalities in PTSD has opened up new ways for understanding the neuronal filters concerned with the interpretation of sensory information in PTSD. These studies have produced a number of unexpected findings, which may alter how we conceptualize PTSD and which may force us to reevaluate appropriate therapeutic interventions.

  10. Post-Traumatic Stress Disorder

    MedlinePlus

    ... Mind and Body Approaches for Health Problems Facing Military Personnel and Veterans Research Spotlights Acupuncture May Help Symptoms ... Mind and Body Approaches for Health Problems in Military Personnel and Veterans Clinical Digest: Stress and Relaxation Techniques ...

  11. Acute Stress Disorder as a Predictor of Post-Traumatic Stress Disorder in Physical Assault Victims

    ERIC Educational Resources Information Center

    Elklit, Ask; Brink, Ole

    2004-01-01

    The authors' objective was to examine the ability of acute stress disorder (ASD) and other trauma-related factors in a group of physical assault victims in predicting post-traumatic stress disorder (PTSD) 6 months later. Subjects included 214 victims of violence who completed a questionnaire 1 to 2 weeks after the assault, with 128 participating…

  12. The Relationship between Acute Stress Disorder and Posttraumatic Stress Disorder Following Cancer

    ERIC Educational Resources Information Center

    Kangas, Maria; Henry, Jane L.; Bryant, Richard A.

    2005-01-01

    In this study, the authors investigated the relationship between acute stress disorder (ASD) and posttraumatic stress disorder (PTSD) following cancer diagnosis. Patients who were recently diagnosed with 1st onset head and neck or lung malignancy (N = 82) were assessed for ASD within the initial month following their diagnosis and reassessed (n =…

  13. The Relationship between Acute Stress Disorder and Posttraumatic Stress Disorder Following Cancer

    ERIC Educational Resources Information Center

    Kangas, Maria; Henry, Jane L.; Bryant, Richard A.

    2005-01-01

    In this study, the authors investigated the relationship between acute stress disorder (ASD) and posttraumatic stress disorder (PTSD) following cancer diagnosis. Patients who were recently diagnosed with 1st onset head and neck or lung malignancy (N = 82) were assessed for ASD within the initial month following their diagnosis and reassessed (n =…

  14. Acute Stress Disorder as a Predictor of Post-Traumatic Stress Disorder in Physical Assault Victims

    ERIC Educational Resources Information Center

    Elklit, Ask; Brink, Ole

    2004-01-01

    The authors' objective was to examine the ability of acute stress disorder (ASD) and other trauma-related factors in a group of physical assault victims in predicting post-traumatic stress disorder (PTSD) 6 months later. Subjects included 214 victims of violence who completed a questionnaire 1 to 2 weeks after the assault, with 128 participating…

  15. Does Acute Stress Disorder Predict Posttraumatic Stress Disorder Following Bank Robbery?

    ERIC Educational Resources Information Center

    Hansen, Maj; Elklit, Ask

    2013-01-01

    Unfortunately, the number of bank robberies is increasing and little is known about the subsequent risk of posttraumatic stress disorder (PTSD). Several studies have investigated the prediction of PTSD through the presence of acute stress disorder (ASD). However, there have only been a few studies following nonsexual assault. The present study…

  16. Does Acute Stress Disorder Predict Posttraumatic Stress Disorder Following Bank Robbery?

    ERIC Educational Resources Information Center

    Hansen, Maj; Elklit, Ask

    2013-01-01

    Unfortunately, the number of bank robberies is increasing and little is known about the subsequent risk of posttraumatic stress disorder (PTSD). Several studies have investigated the prediction of PTSD through the presence of acute stress disorder (ASD). However, there have only been a few studies following nonsexual assault. The present study…

  17. Cortisol stress response in post-traumatic stress disorder, panic disorder, and major depressive disorder patients.

    PubMed

    Wichmann, Susann; Kirschbaum, Clemens; Böhme, Carsten; Petrowski, Katja

    2017-09-01

    Previous research has focussed extensively on the distinction of HPA-axis functioning between patient groups and healthy volunteers, with relatively little emphasis on a direct comparison of patient groups. The current study's aim was to analyse differences in the cortisol stress response as a function of primary diagnosis of panic disorder (PD), post-traumatic stress disorder (PTSD), and major depressive disorder (MDD). A total of n=30 PD (mean age±SD: 36.07±12.56), n=23 PTSD (41.22±10.17), n=18 MDD patients (39.00±14.93) and n=47 healthy control (HC) individuals (35.51±13.15) participated in this study. All the study participants were female. The Trier Social Stress Test (TSST) was used for reliable laboratory stress induction. Blood sampling accompanied the TSST for cortisol and ACTH assessment. Panic-related, PTSD-specific questionnaires and the Beck Depression Inventory II were handed out for the characterisation of the study groups. Repeated measure ANCOVAs were conducted to test for main effects of time or group and for interaction effects. Regression analyses were conducted to take comorbid depression into account. 26.7% of the PD patients, 43.5% of the PTSD patients, 72.2% of the MDD patients and 80.6% of the HC participants showed a cortisol stress response upon the TSST. ANCOVA revealed a cortisol hypo-responsiveness both in PD and PTSD patients, while no significant group differences were seen in the ACTH concentrations. Additional analyses showed no impact of comorbid depressiveness on the cortisol stress response. MDD patients did not differ in the hormonal stress response neither compared to the HC participants nor to the PD and PTSD patients. Our main findings provide evidence of a dissociation between the cortisol and ACTH concentrations in response to the TSST in PTSD and in PD patients, independent of comorbid depression. Our results further support overall research findings of a cortisol hypo-responsiveness in PD patients. A hypo

  18. Lower Electrodermal Activity to Acute Stress in Caregivers of People with Autism Spectrum Disorder: An Adaptive Habituation to Stress

    ERIC Educational Resources Information Center

    Ruiz-Robledillo, Nicolás; Moya-Albiol, Luis

    2015-01-01

    Caring for a relative with autism spectrum disorder (ASD) entails being under chronic stress that could alter body homeostasis. Electrodermal activity (EDA) is an index of the sympathetic activity of the autonomic nervous system related to emotionality and homeostasis. This study compares EDA in response to acute stress in the laboratory between…

  19. Lower Electrodermal Activity to Acute Stress in Caregivers of People with Autism Spectrum Disorder: An Adaptive Habituation to Stress

    ERIC Educational Resources Information Center

    Ruiz-Robledillo, Nicolás; Moya-Albiol, Luis

    2015-01-01

    Caring for a relative with autism spectrum disorder (ASD) entails being under chronic stress that could alter body homeostasis. Electrodermal activity (EDA) is an index of the sympathetic activity of the autonomic nervous system related to emotionality and homeostasis. This study compares EDA in response to acute stress in the laboratory between…

  20. Genome-wide alterations in hippocampal 5-hydroxymethylcytosine links plasticity genes to acute stress

    PubMed Central

    Li, Sisi; Papale, Ligia A.; Zhang, Qi; Madrid, Andy; Chen, Li; Chopra, Pankaj; Keleş, Sündüz; Jin, Peng; Alisch, Reid S.

    2015-01-01

    Environmental stress is among the most important contributors to increased susceptibility to develop psychiatric disorders, including anxiety and post-traumatic stress disorder. While even acute stress alters gene expression, the molecular mechanisms underlying these changes remain largely unknown. 5-hydroxymethylcytosine (5hmC) is a novel environmentally sensitive DNA modification that is highly enriched in post-mitotic neurons and is associated with active transcription of neuronal genes. Recently, we found a hippocampal increase of 5hmC in the glucocorticoid receptor gene (Nr3c1) following acute stress, warranting a deeper investigation of stress-related 5hmC levels. Here, we used an established chemical labeling and affinity purification method coupled with high-throughput sequencing technology to generate the first genome-wide profile of hippocampal 5hmC following exposure to acute restraint stress and a one-hour recovery. This approach found a genome-wide disruption in 5hmC associated with acute stress response, primarily in genic regions, and identified known and potentially novel stress-related targets that have a significant enrichment for neuronal ontological functions. Integration of these data with hippocampal gene expression data from these same mice found stress-related hydroxymethylation correlated to altered transcript levels and sequence motif predictions indicated that 5hmC may function by mediating transcription factor binding to these transcripts. Together, these data reveal an environmental impact on this newly discovered epigenetic mark in the brain and represent a critical step toward understanding stress-related epigenetic mechanisms that alter gene expression and can lead to the development of psychiatric disorders. PMID:26598390

  1. Anxiety, stress and perfectionism in bipolar disorder.

    PubMed

    Corry, Justine; Green, Melissa; Roberts, Gloria; Frankland, Andrew; Wright, Adam; Lau, Phoebe; Loo, Colleen; Breakspear, Michael; Mitchell, Philip B

    2013-12-01

    Previous reports have highlighted perfectionism and related cognitive styles as a psychological risk factor for stress and anxiety symptoms as well as for the development of bipolar disorder symptoms. The anxiety disorders are highly comorbid with bipolar disorder but the mechanisms that underpin this comorbidity are yet to be determined. Measures of depressive, (hypo)manic, anxiety and stress symptoms and perfectionistic cognitive style were completed by a sample of 142 patients with bipolar disorder. Mediation models were used to explore the hypotheses that anxiety and stress symptoms would mediate relationships between perfectionistic cognitive styles, and bipolar disorder symptoms. Stress and anxiety both significantly mediated the relationship between both self-critical perfectionism and goal attainment values and bipolar depressive symptoms. Goal attainment values were not significantly related to hypomanic symptoms. Stress and anxiety symptoms did not significantly mediate the relationship between self-critical perfectionism and (hypo)manic symptoms. 1. These data are cross-sectional; hence the causality implied in the mediation models can only be inferred. 2. The clinic patients were less likely to present with (hypo)manic symptoms and therefore the reduced variability in the data may have contributed to the null findings for the mediation models with (hypo) manic symptoms. 3. Those patients who were experiencing current (hypo)manic symptoms may have answered the cognitive styles questionnaires differently than when euthymic. These findings highlight a plausible mechanism to understand the relationship between bipolar disorder and the anxiety disorders. Targeting self-critical perfectionism in the psychological treatment of bipolar disorder when there is anxiety comorbidity may result in more parsimonious treatments. © 2013 Published by Elsevier B.V.

  2. Comorbidity of psychiatric disorders and posttraumatic stress disorder.

    PubMed

    Brady, K T; Killeen, T K; Brewerton, T; Lucerini, S

    2000-01-01

    Posttraumatic stress disorder (PTSD) commonly co-occurs with other psychiatric disorders. Data from epidemiologic surveys indicate that the vast majority of individuals with PTSD meet criteria for at least one other psychiatric disorder, and a substantial percentage have 3 or more other psychiatric diagnoses. A number of different hypothetical constructs have been posited to explain this high comorbidity; for example, the self-medication hypothesis has often been applied to understand the relationship between PTSD and substance use disorders. There is a substantial amount of symptom overlap between PTSD and a number of other psychiatric diagnoses, particularly major depressive disorder. It has been suggested that high rates of comorbidity may be simply an epiphenomenon of the diagnostic criteria used. In any case, this high degree of symptom overlap can contribute to diagnostic confusion and, in particular, to the underdiagnosis of PTSD when trauma histories are not specifically obtained. The most common comorbid diagnoses are depressive disorders, substance use disorders, and other anxiety disorders. The comorbidity of PTSD and depressive disorders is of particular interest. Across a number of studies, these are the disorders most likely to co-occur with PTSD. It is also clear that depressive disorder can be a common and independent sequela of exposure to trauma and having a previous depressive disorder is a risk factor for the development of PTSD once exposure to a trauma occurs. The comorbidity of PTSD with substance use disorders is complex because while a substance use disorder may often develop as an attempt to self-medicate the painful symptoms of PTSD, withdrawal states exaggerate these symptoms. Appropriate treatment of PTSD in substance abusers is a controversial issue because of the belief that addressing issues related to the trauma in early recovery can precipitate relapse. In conclusion, comorbidity in PTSD is the rule rather than the exception. This

  3. Cognitive Disruptions in Stress-Related Psychiatric Disorders: A Role for Corticotropin Releasing Factor (CRF)

    PubMed Central

    Bangasser, Debra A.; Kawasumi, Yushi

    2015-01-01

    Stress is a potential etiology contributor to both post-traumatic stress disorders (PTSD) and major depression. One stress-related neuropeptide that is hypersecreted in these disorders is corticotropin releasing factor (CRF). Dysregulation of CRF has long been linked to the emotion and mood symptoms that characterize PTSD and depression. However, the idea that CRF also mediates the cognitive disruptions observed in patients with these disorders has received less attention. Here we review literature indicating that CRF can alter cognitive functions. Detailed are anatomical studies revealing that CRF is poised to modulate regions required for learning and memory. We also describe preclinical behavioral studies that demonstrate CRF’s ability to alter fear conditioning, impair memory consolidation, and alter a number of executive functions, including attention and cognitive flexibility. The implications of these findings for the etiology and treatment of the cognitive impairments observed in stress-related psychiatric disorders are described. PMID:25888454

  4. Repeated swim stress alters brain benzodiazepine receptors measured in vivo

    SciTech Connect

    Weizman, R.; Weizman, A.; Kook, K.A.; Vocci, F.; Deutsch, S.I.; Paul, S.M.

    1989-06-01

    The effects of repeated swim stress on brain benzodiazepine receptors were examined in the mouse using both an in vivo and in vitro binding method. Specific in vivo binding of (/sup 3/H)Ro15-1788 to benzodiazepine receptors was decreased in the hippocampus, cerebral cortex, hypothalamus, midbrain and striatum after repeated swim stress (7 consecutive days of daily swim stress) when compared to nonstressed mice. In vivo benzodiazepine receptor binding was unaltered after repeated swim stress in the cerebellum and pons medulla. The stress-induced reduction in in vivo benzodiazepine receptor binding did not appear to be due to altered cerebral blood flow or to an alteration in benzodiazepine metabolism or biodistribution because there was no difference in (14C)iodoantipyrine distribution or whole brain concentrations of clonazepam after repeated swim stress. Saturation binding experiments revealed a change in both apparent maximal binding capacity and affinity after repeated swim stress. Moreover, a reduction in clonazepam's anticonvulsant potency was also observed after repeated swim stress (an increase in the ED50 dose for protection against pentylenetetrazol-induced seizures), although there was no difference in pentylenetetrazol-induced seizure threshold between the two groups. In contrast to the results obtained in vivo, no change in benzodiazepine receptor binding kinetics was observed using the in vitro binding method. These data suggest that environmental stress can alter the binding parameters of the benzodiazepine receptor and that the in vivo and in vitro binding methods can yield substantially different results.

  5. Post-Traumatic Stress Disorder

    MedlinePlus

    ... a traumatic event, such as war, a hurricane, sexual assault, physical abuse, or a bad accident. PTSD makes you feel stressed and afraid after the danger is over. It affects your life and the people around you. PTSD can cause problems like Flashbacks, or feeling like the event ...

  6. Oxidative Stress and Neurodegenerative Disorders

    PubMed Central

    Li, Jie; O, Wuliji; Li, Wei; Jiang, Zhi-Gang; Ghanbari, Hossein A.

    2013-01-01

    Living cells continually generate reactive oxygen species (ROS) through the respiratory chain during energetic metabolism. ROS at low or moderate concentration can play important physiological roles. However, an excessive amount of ROS under oxidative stress would be extremely deleterious. The central nervous system (CNS) is particularly vulnerable to oxidative stress due to its high oxygen consumption, weakly antioxidative systems and the terminal-differentiation characteristic of neurons. Thus, oxidative stress elicits various neurodegenerative diseases. In addition, chemotherapy could result in severe side effects on the CNS and peripheral nervous system (PNS) of cancer patients, and a growing body of evidence demonstrates the involvement of ROS in drug-induced neurotoxicities as well. Therefore, development of antioxidants as neuroprotective drugs is a potentially beneficial strategy for clinical therapy. In this review, we summarize the source, balance maintenance and physiologic functions of ROS, oxidative stress and its toxic mechanisms underlying a number of neurodegenerative diseases, and the possible involvement of ROS in chemotherapy-induced toxicity to the CNS and PNS. We ultimately assess the value for antioxidants as neuroprotective drugs and provide our comments on the unmet needs. PMID:24351827

  7. Posttraumatic stress disorder and traumatic stress: from bench to bedside, from war to disaster.

    PubMed

    Ursano, Robert J; Goldenberg, Matthew; Zhang, Lei; Carlton, Janis; Fullerton, Carol S; Li, He; Johnson, Luke; Benedek, David

    2010-10-01

    War is a tragic event and its mental health consequences can be profound. Recent studies indicate substantial rates of posttraumatic stress disorder and other behavioral alterations because of war exposure. Understanding the psychological, behavioral, and neurobiological mechanism of mental health and behavioral changes related to war exposure is critical to helping those in need of care. Substantial work to encourage bench to bedside to community knowledge and communication is a core component of addressing this world health need.

  8. Late-onset posttraumatic stress disorder.

    PubMed

    Snyder, Marsha

    2008-11-01

    Posttraumatic stress disorder (PTSD) is a complex psychological response to a perceived life-threatening trauma that includes re-experiencing the trauma, avoidance, intrusive thoughts, hyperarousal, and dissociation. Exposure to trauma in early adulthood increases the potential for further psychological threats throughout life. In older adult populations, PTSD is an underrecognized and undertreated disorder that can result in psychosocial disability, substance use, and other negative health outcomes. This article examines the range of symptoms related to PTSD in older adults and expands on health care provider sensitivity to the interrelationship of mental and physical health when addressing the needs of older adults with this disorder.

  9. Host stress hormones alter vector feeding preferences, success, and productivity

    PubMed Central

    Burkett-Cadena, Nathan; Burgan, Sarah C.; Schrey, Aaron W.; Hassan, Hassan K.; Unnasch, Thomas R.; Martin, Lynn B.

    2016-01-01

    Stress hormones might represent a key link between individual-level infection outcome, population-level parasite transmission, and zoonotic disease risk. Although the effects of stress on immunity are well known, stress hormones could also affect host–vector interactions via modification of host behaviours or vector-feeding patterns and subsequent reproductive success. Here, we experimentally manipulated songbird stress hormones and examined subsequent feeding preferences, feeding success, and productivity of mosquito vectors in addition to defensive behaviours of hosts. Despite being more defensive, birds with elevated stress hormone concentrations were approximately twice as likely to be fed on by mosquitoes compared to control birds. Moreover, stress hormones altered the relationship between the timing of laying and clutch size in blood-fed mosquitoes. Our results suggest that host stress could affect the transmission dynamics of vector-borne parasites via multiple pathways. PMID:27512147

  10. Host stress hormones alter vector feeding preferences, success, and productivity.

    PubMed

    Gervasi, Stephanie S; Burkett-Cadena, Nathan; Burgan, Sarah C; Schrey, Aaron W; Hassan, Hassan K; Unnasch, Thomas R; Martin, Lynn B

    2016-08-17

    Stress hormones might represent a key link between individual-level infection outcome, population-level parasite transmission, and zoonotic disease risk. Although the effects of stress on immunity are well known, stress hormones could also affect host-vector interactions via modification of host behaviours or vector-feeding patterns and subsequent reproductive success. Here, we experimentally manipulated songbird stress hormones and examined subsequent feeding preferences, feeding success, and productivity of mosquito vectors in addition to defensive behaviours of hosts. Despite being more defensive, birds with elevated stress hormone concentrations were approximately twice as likely to be fed on by mosquitoes compared to control birds. Moreover, stress hormones altered the relationship between the timing of laying and clutch size in blood-fed mosquitoes. Our results suggest that host stress could affect the transmission dynamics of vector-borne parasites via multiple pathways.

  11. Animal models of anxiety disorders and stress.

    PubMed

    Campos, Alline C; Fogaça, Manoela V; Aguiar, Daniele C; Guimarães, Francisco S

    2013-01-01

    Anxiety and stress-related disorders are severe psychiatric conditions that affect performance in daily tasks and represent a high cost to public health. The initial observation of Charles Darwin that animals and human beings share similar characteristics in the expression of emotion raise the possibility of studying the mechanisms of psychiatric disorders in other mammals (mainly rodents). The development of animal models of anxiety and stress has helped to identify the pharmacological mechanisms and potential clinical effects of several drugs. Animal models of anxiety are based on conflict situations that can generate opposite motivational states induced by approach-avoidance situations. The present review revisited the main rodent models of anxiety and stress responses used worldwide. Here we defined as "ethological" the tests that assess unlearned/unpunished responses (such as the elevated plus maze, light-dark box, and open field), whereas models that involve learned/punished responses are referred to as "conditioned operant conflict tests" (such as the Vogel conflict test). We also discussed models that involve mainly classical conditioning tests (fear conditioning). Finally, we addressed the main protocols used to induce stress responses in rodents, including psychosocial (social defeat and neonatal isolation stress), physical (restraint stress), and chronic unpredictable stress.

  12. Which Vietnam Veterans Develop Posttraumatic Stress Disorders?

    ERIC Educational Resources Information Center

    Solkoff, Norman; And Others

    1986-01-01

    Vietnam combat veterans diagnosed as having Postraumatic Stress Disorder (PTSD) differed significantly in the intensity of their combat experiences and their perceptions of their homecoming experiences from controls who were also combat veterans. Neither early history nor immediate preservice factors differentiated the two groups. (Author/KS)

  13. Traumatic brain injury and posttraumatic stress disorder.

    PubMed

    Bahraini, Nazanin H; Breshears, Ryan E; Hernández, Theresa D; Schneider, Alexandra L; Forster, Jeri E; Brenner, Lisa A

    2014-03-01

    Given the upsurge of research in posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI), much of which has focused on military samples who served in Iraq and Afghanistan, the purpose of this article is to review the literature published after September 11th, 2001 that addresses the epidemiology, pathophysiology, evaluation, and treatment of PTSD in the context of TBI.

  14. Pharmacotherapy of post-traumatic stress disorder.

    PubMed

    Opler, Lewis A; Grennan, Michelle S; Opler, Mark G

    2006-12-01

    In the Diagnostic and Statistical Manual of Mental Disorders (DSM)-III, DSM-III-R and DSM-IV, the diagnosis of post-traumatic stress disorder (PTSD) requires the presence of three symptom clusters: re-experiencing, avoidance and hyperarousal. The selective serotonin reuptake inhibitors (SSRIs), in particular sertraline and paroxetine, have emerged as the treatment of choice for trauma victims experiencing these three symptom clusters. While not approved by the U.S. Food and Drug Administration, other pharmacological agents are often used, some for symptoms found in victims of early, chronic or extreme stress. Referred to as having type II trauma, complex PTSD, disorders of extreme stress and enduring personality change after catastrophic experience, these patients, with symptoms such as dissociation, somatization and self-injurious behavior, need to be recognized as suffering from a trauma-related disorder qualitatively different from that presently captured in the DSM-IV. In this paper we will refer to DSM-IV's construct as simple PTSD (sPTSD); to complex PTSD/disorders of extreme stress as cPTSD/DES; and to both as PTSD. We will review existing evidence for the efficacy of SSRIs in treating sPTSD as well as different pharmacological interventions that are necessary for the treatment of cPTSD/DES. In addition, since both sPTSD and cPTSD/DES frequently coexist with other mental disorders, treatment of comorbid PTSD will be addressed. Finally, given that existing rating scales are not designed to measure symptoms of cPTSD/DES, we will describe the Symptoms of Trauma Scale (SOTS), designed to measure symptoms of both sPTSD and cPTSD. Copyright (c) 2006 Prous Science. All rights reserved.

  15. Review of somatic symptoms in post-traumatic stress disorder.

    PubMed

    Gupta, Madhulika A

    2013-02-01

    Post-traumatic stress disorder (PTSD) is associated with both (1) 'ill-defined' or 'medically unexplained' somatic syndromes, e.g. unexplained dizziness, tinnitus and blurry vision, and syndromes that can be classified as somatoform disorders (DSM-IV-TR); and (2) a range of medical conditions, with a preponderance of cardiovascular, respiratory, musculoskeletal, neurological, and gastrointestinal disorders, diabetes, chronic pain, sleep disorders and other immune-mediated disorders in various studies. Frequently reported medical co-morbidities with PTSD across various studies include cardiovascular disease, especially hypertension, and immune-mediated disorders. PTSD is associated with limbic instability and alterations in both the hypothalamic- pituitary-adrenal and sympatho-adrenal medullary axes, which affect neuroendocrine and immune functions, have central nervous system effects resulting in pseudo-neurological symptoms and disorders of sleep-wake regulation, and result in autonomic nervous system dysregulation. Hypervigilance, a central feature of PTSD, can lead to 'local sleep' or regional arousal states, when the patient is partially asleep and partially awake, and manifests as complex motor and/or verbal behaviours in a partially conscious state. The few studies of the effects of standard PTSD treatments (medications, CBT) on PTSD-associated somatic syndromes report a reduction in the severity of ill-defined and autonomically mediated somatic symptoms, self-reported physical health problems, and some chronic pain syndromes.

  16. Altered Gravity Induces Oxidative Stress in Drosophila Melanogaster

    NASA Technical Reports Server (NTRS)

    Bhattacharya, Sharmila; Hosamani, Ravikumar

    2015-01-01

    Altered gravity environments can induce increased oxidative stress in biological systems. Microarray data from our previous spaceflight experiment (FIT experiment on STS-121) indicated significant changes in the expression of oxidative stress genes in adult fruit flies after spaceflight. Currently, our lab is focused on elucidating the role of hypergravity-induced oxidative stress and its impact on the nervous system in Drosophila melanogaster. Biochemical, molecular, and genetic approaches were combined to study this effect on the ground. Adult flies (2-3 days old) exposed to acute hypergravity (3g, for 1 hour and 2 hours) showed significantly elevated levels of Reactive Oxygen Species (ROS) in fly brains compared to control samples. This data was supported by significant changes in mRNA expression of specific oxidative stress and antioxidant defense related genes. As anticipated, a stress-resistant mutant line, Indy302, was less vulnerable to hypergravity-induced oxidative stress compared to wild-type flies. Survival curves were generated to study the combined effect of hypergravity and pro-oxidant treatment. Interestingly, many of the oxidative stress changes that were measured in flies showed sex specific differences. Collectively, our data demonstrate that altered gravity significantly induces oxidative stress in Drosophila, and that one of the organs where this effect is evident is the brain.

  17. Larval environmental stress alters Aedes aegypti competence for Sindbis virus.

    PubMed

    Muturi, Ephantus J; Kim, Chang-Hyun; Alto, Barry W; Berenbaum, May R; Schuler, Mary A

    2011-08-01

    To evaluate how stress at the larval stage alters adult mosquito performance and susceptibility to viral infection. We used a model system consisting of Sindbis virus (SINV) and the yellow fever mosquito Aedes aegypti. Larvae were either reared under optimal conditions (control) or exposed to one of four types of stressors; suboptimal nutrients, starvation, elevated temperature, and a low dose of the insecticide malathion and adult females were fed SINV infectious blood meal. Differential expressions of stress, immune-specific and detoxification genes was measured in fourth instar larvae (HSP70, HSP83, cecropin, defensin, transferrin and CYP6Z6) and 3-day-old females (cecropin, defensin, transferrin) to identify plausible molecular mechanisms associated with mosquito response to stress. There were stress-specific variations in mosquito performance (survival, development time, female size), but all stressors had a consistent effect of significantly increasing susceptibility to viral infection and dissemination relative to the controls. Three genes were up-regulated in fourth instar larvae exposed to temperature stress (cecropin, defensin and CYP6Z6) compared to single genes in suboptimal nutrient (cecropin) and malathion (transferrin) stress treatments and down-regulation of all the six genes in starvation treatments. In adult samples, transferrin was up-regulated in all but starvation treatments while defensin was up-regulated in starvation and temperature stress treatments. Stress during larval development may cause alterations in adult mosquito phenotype and immunity that can increase their susceptibility to pathogens. © 2011 Blackwell Publishing Ltd.

  18. Multimodal Approach to Identifying Malingered Posttraumatic Stress Disorder: A Review

    PubMed Central

    Jabeen, Shagufta; Alam, Farzana

    2015-01-01

    The primary aim of this article is to aid clinicians in differentiating true posttraumatic stress disorder from malingered posttraumatic stress disorder. Posttraumatic stress disorder and malingering are defined, and prevalence rates are explored. Similarities and differences in diagnostic criteria between the fourth and fifth editions of the Diagnostic and Statistical Manual of Mental Disorders are described for posttraumatic stress disorder. Possible motivations for malingering posttraumatic stress disorder are discussed, and common characteristics of malingered posttraumatic stress disorder are described. A multimodal approach is described for evaluating posttraumatic stress disorder, including interview techniques, collection of collateral data, and psychometric and physiologic testing, that should allow clinicians to distinguish between those patients who are truly suffering from posttraumatic disorder and those who are malingering the illness. PMID:25852974

  19. Multimodal approach to identifying malingered posttraumatic stress disorder: a review.

    PubMed

    Ali, Shahid; Jabeen, Shagufta; Alam, Farzana

    2015-01-01

    The primary aim of this article is to aid clinicians in differentiating true posttraumatic stress disorder from malingered posttraumatic stress disorder. Posttraumatic stress disorder and malingering are defined, and prevalence rates are explored. Similarities and differences in diagnostic criteria between the fourth and fifth editions of the Diagnostic and Statistical Manual of Mental Disorders are described for posttraumatic stress disorder. Possible motivations for malingering posttraumatic stress disorder are discussed, and common characteristics of malingered posttraumatic stress disorder are described. A multimodal approach is described for evaluating posttraumatic stress disorder, including interview techniques, collection of collateral data, and psychometric and physiologic testing, that should allow clinicians to distinguish between those patients who are truly suffering from posttraumatic disorder and those who are malingering the illness.

  20. Learning and memory in Holocaust survivors with posttraumatic stress disorder.

    PubMed

    Yehuda, Rachel; Golier, Julia A; Halligan, Sarah L; Harvey, Philip D

    2004-02-01

    Impairments in explicit memory have been observed in Holocaust survivors with posttraumatic stress disorder. To evaluate which memory components are preferentially affected, the California Verbal Learning Test was administered to Holocaust survivors with (n = 36) and without (n = 26) posttraumatic stress disorder, and subjects not exposed to the Holocaust (n = 40). Posttraumatic stress disorder subjects showed impairments in learning and short-term and delayed retention compared to nonexposed subjects; survivors without posttraumatic stress disorder did not. Impairments in learning, but not retention, were retained after controlling for intelligence quotient. Older age was associated with poorer learning and memory performance in the posttraumatic stress disorder group only. The most robust impairment observed in posttraumatic stress disorder was in verbal learning, which may be a risk factor for or consequence of chronic posttraumatic stress disorder. The negative association between performance and age may reflect accelerated cognitive decline in posttraumatic stress disorder.

  1. Post-traumatic Stress Disorder Post Partum

    PubMed Central

    Schwab, W.; Marth, C.; Bergant, A. M.

    2012-01-01

    Traumatic birth experiences may lead to serious psychological impairment. Recent studies show that a considerable number of women can develop post-traumatic stress disorder (PTSD), in some cases in a subsyndromal form. Until now, the possibility that postpartum psychological symptoms might be a continuum of a pre-existing disorder in pregnancy has rarely been considered. This study therefore aimed to evaluate the proportion of women who develop post-traumatic stress disorder as a result of childbirth. Materials and Methods: 56 multiparous women were recruited for the study. The diagnosis of PTSD was made according to the criteria for psychological disorders in the DSM-IV (Diagnostics and Statistical Manual of Mental Disorders). The data were collected in structured interviews in the 30th to 38th week of gestation and in the 6th week post partum. Results: Of the 56 women participating, 52 (93 %) completed the survey. Uncontrolled results showed that 21.15 % of the multiparous women met the full diagnostic PTSD criteria in the 6th week post partum. After the exclusion of all cases already characterised by all criteria or a subsyndromal form of PTSD caused by previous traumatisation, the PTSD rate was below 8 % at 6 weeks postpartum (= incidence rate of PTSD post partum). Conclusions: The present study is the first prospective longitudinal study to demonstrate the occurrence of full criteria PTSD in multiparous women as a result of childbirth after having excluded pre-existing PTSD. The results of our study show a high prevalence rate of PTSD during pregnancy. A number of women report all aspects of post-traumatic stress disorder as a result of childbirth. PMID:25253905

  2. Salt stress alters the cell wall polysaccharides and anatomy of coffee (Coffea arabica L.) leaf cells.

    PubMed

    de Lima, Rogério Barbosa; dos Santos, Tiago Benedito; Vieira, Luiz Gonzaga Esteves; de Lourdes Lúcio Ferrarese, Maria; Ferrarese-Filho, Osvaldo; Donatti, Lucélia; Boeger, Maria Regina Torres; de Oliveira Petkowicz, Carmen Lúcia

    2014-11-04

    Coffea arabica is the most important agricultural commodity in the world, and salinity is a major threat to its sustainable irrigation. Coffee leaf polysaccharides from plants subjected to salt stress were extracted and the leaves visualized through optical and electron microscopy. Alterations were detected in the monosaccharide composition of the pectin and hemicelluloses, with increases in uronic acid in all fractions. Changes in the polysaccharides were confirmed by HPSEC and FTIR. Moreover, the monolignol content was increased in the final residue, which suggests increased lignin content. The cytoplasm was altered, and the chloroplasts appeared irregular in shape. The arrangement of the stroma lamellae was disordered, and no starch granules were present. It was concluded that leaves of C. arabica under salt stress showed alterations in cell wall polysaccharides, increased monolignol content and structural damage to the cells of the mesophyll.

  3. Neuropeptide Y and posttraumatic stress disorder

    PubMed Central

    Sah, R; Geracioti, TD

    2016-01-01

    Resiliency to the adverse effects of extraordinary emotional trauma on the brain varies within the human population. Accordingly, some people cope better than others with traumatic stress. Neuropeptide Y (NPY) is a 36-amino-acid peptide transmitter abundantly expressed in forebrain limbic and brain stem areas that regulate stress and emotional behaviors. Studies largely in rodents demonstrate a role for NPY in promoting coping with stress. Moreover, accruing data from the genetic to the physiological implicate NPY as a potential ‘resilience-to-stress’ factor in humans. Here, we consolidate findings from preclinical and clinical studies of NPY that are of relevance to stress-associated syndromes, most prototypically posttraumatic stress disorder (PTSD). Collectively, these data suggest that reduced central nervous system (CNS) NPY concentrations or function may be associated with PTSD. We also link specific symptoms of human PTSD with extant findings in the NPY field to reveal potential physiological contributions of the neuropeptide to the disorder. In pursuit of understanding the physiological basis and treatment of PTSD, the NPY system is an attractive target. PMID:22801411

  4. Investigation of Stress Induced Alterations in Neutrophil Function

    DTIC Science & Technology

    1990-04-23

    defense against bacterial incursion and to examine the effects on this cell in two biological systems of stress effects including 1) a week - long...response of neutrophils from the matched controls indicating that migration capability may not represent a function altered by the psycological and

  5. College Student Stress: A Predictor of Eating Disorder Precursor Behaviors

    ERIC Educational Resources Information Center

    Shelton, Virginia L.; Valkyrie, Karena T.

    2010-01-01

    Eating disorders are compulsive behaviors that can consume a person's life to the point of becoming life threatening. Previous research found stress associated with eating disorders. College can be a stressful time. If stress predicted precursor behaviors to eating disorders, then counselors would have a better chance to help students sooner. This…

  6. The Root Cause of Post-traumatic and Developmental Stress Disorder

    DTIC Science & Technology

    2011-03-01

    patient recruitment on a therapeutic trial of the serotonin reuptake inhibitor fluoxetine , to determine whether it can alter the trajectory of post...influencing resiliency and susceptibility to stress disorders and therapeutic response to fluoxetine . A panel of 15 genes has been tested and...Progress 03/29/11 Redesigned by recommendation of TATRC review process Project 2 Fluoxetine for post-deployment stress disorder Task 1

  7. Psychologic trauma, posttraumatic stress disorder, and dermatology.

    PubMed

    Gupta, Madhulika A; Lanius, Ruth A; Van der Kolk, Bessel A

    2005-10-01

    Psychologic trauma refers to events (such as sexual assault, major earthquake, or plane crashes) that overwhelm an individual's capacity to cope. Psychologic trauma can result in chronic and recurring dermatologic symptoms that persist after the trauma subsides. Examples are cutaneous sensory flashbacks (which may be fragments of the sensory component of the traumatic experience), autonomic hyperarousal (with symptoms such as profuse sweating or flare-up of an underlying stress-reactive dermatosis), conversion symptoms (such as numbness, pain, or other medically unexplained cutaneous symptoms), and cutaneous self-injury (manifesting in many forms, including trichotillomania, dermatitis artefacta, and neurotic excoriations--tension-reducing behaviors in patients who have posttraumatic stress disorder).

  8. Posttraumatic Stress Disorder (PTSD) and Disorders of Extreme Stress (DESNOS) symptoms following prostitution and childhood abuse.

    PubMed

    Choi, Hyunjung; Klein, Carolin; Shin, Min-Sup; Lee, Hoon-Jin

    2009-08-01

    With the participation of 46 prostituted women in Korea, this study investigates the relationship between prostitution experiences, a history of childhood sexual abuse (CSA), and symptoms of posttraumatic stress disorder (PTSD) and disorders of extreme stress not otherwise specified (DESNOS). Prostituted women showed higher levels of PTSD and DESNOS symptoms compared to a control group. Women who had experienced both CSA by a significant other and prostitution showed the highest levels of traumatic stress. However, posttraumatic reexperiencing and avoidance and identity, relational, and affect regulation problems were significant for prostitution experiences even when the effects of CSA were controlled.

  9. Aging induced endoplasmic reticulum stress alters sleep and sleep homeostasis.

    PubMed

    Brown, Marishka K; Chan, May T; Zimmerman, John E; Pack, Allan I; Jackson, Nicholas E; Naidoo, Nirinjini

    2014-06-01

    Alterations in the quality, quantity, and architecture of baseline and recovery sleep have been shown to occur during aging. Sleep deprivation induces endoplasmic reticular (ER) stress and upregulates a protective signaling pathway termed the unfolded protein response. The effectiveness of the adaptive unfolded protein response is diminished by age. Previously, we showed that endogenous chaperone levels altered recovery sleep in Drosophila melanogaster. We now report that acute administration of the chemical chaperone sodium 4-phenylbutyrate (PBA) reduces ER stress and ameliorates age-associated sleep changes in Drosophila. PBA consolidates both baseline and recovery sleep in aging flies. The behavioral modifications of PBA are linked to its suppression of ER stress. PBA decreased splicing of X-box binding protein 1 and upregulation of phosphorylated elongation initiation factor 2 α, in flies that were subjected to sleep deprivation. We also demonstrate that directly activating ER stress in young flies fragments baseline sleep and alters recovery sleep. Alleviating prolonged or sustained ER stress during aging contributes to sleep consolidation and improves recovery sleep or sleep debt discharge.

  10. Aging induced ER stress alters sleep and sleep homeostasis

    PubMed Central

    Brown, Marishka K.; Chan, May T.; Zimmerman, John E.; Pack, Allan I.; Jackson, Nicholas E.; Naidoo, Nirinjini

    2014-01-01

    Alterations in the quality, quantity and architecture of baseline and recovery sleep have been shown to occur during aging. Sleep deprivation induces endoplasmic reticular (ER) stress and upregulates a protective signaling pathway termed the unfolded protein response (UPR). The effectiveness of the adaptive UPR is diminished by age. Previously, we showed that endogenous chaperone levels altered recovery sleep in Drosophila melanogaster. We now report that acute administration of the chemical chaperone sodium 4-phenylbutyrate (PBA) reduces ER stress and ameliorates age-associated sleep changes in Drosophila. PBA consolidates both baseline and recovery sleep in aging flies. The behavioral modifications of PBA are linked to its suppression of ER stress. PBA decreased splicing of x-box binding protein 1 (XBP1) and upregulation of phosphorylated elongation initiation factor 2 α (p-eIF2α), in flies that were subjected to sleep deprivation. We also demonstrate that directly activating ER stress in young flies fragments baseline sleep and alters recovery sleep. Alleviating prolonged/sustained ER stress during aging contributes to sleep consolidation and improves recovery sleep/ sleep debt discharge. PMID:24444805

  11. Epigenetic signaling in psychiatric disorders: stress and depression

    PubMed Central

    Bagot, Rosemary C.; Labonté, Benoit; Peña, Catherine J.; Nestler, Eric J.

    2014-01-01

    Psychiatric disorders are complex multifactorial disorders involving chronic alterations in neural circuit structure and function. While genetic factors play a role in the etiology of disorders such as depression, addiction, and schizophrenia, relatively high rates of discordance among identical twins clearly point to the importance of additional factors. Environmental factors, such as stress, play a major role in the psychiatric disorders by inducing stable changes in gene expression, neural circuit function, and ultimately behavior. Insults at the developmental stage and in adulthood appear to induce distinct maladaptations. Increasing evidence indicates that these sustained abnormalities are maintained by epigenetic modifications in specific brain regions. Indeed, transcriptional dysregulation and associated aberrant epigenetic regulation is a unifying theme in psychiatric disorders. Aspects of depression can be modeled in animals by inducing disease-like states through environmental manipulations, and these studies can provide a more general understanding of epigenetic mechanisms in psychiatric disorders. Understanding how environmental factors recruit the epigenetic machinery in animal models is providing new insights into disease mechanisms in humans. PMID:25364280

  12. Epigenetic signaling in psychiatric disorders: stress and depression.

    PubMed

    Bagot, Rosemary C; Labonté, Benoit; Peña, Catherine J; Nestler, Eric J

    2014-09-01

    Psychiatric disorders are complex multifactorial disorders involving chronic alterations in neural circuit structure and function. While genetic factors play a role in the etiology of disorders such as depression, addiction, and schizophrenia, relatively high rates of discordance among identical twins clearly point to the importance of additional factors. Environmental factors, such as stress, play a major role in the psychiatric disorders by inducing stable changes in gene expression, neural circuit function, and ultimately behavior. Insults at the developmental stage and in adulthood appear to induce distinct maladaptations. Increasing evidence indicates that these sustained abnormalities are maintained by epigenetic modifications in specific brain regions. Indeed, transcriptional dysregulation and associated aberrant epigenetic regulation is a unifying theme in psychiatric disorders. Aspects of depression can be modeled in animals by inducing disease-like states through environmental manipulations, and these studies can provide a more general understanding of epigenetic mechanisms in psychiatric disorders. Understanding how environmental factors recruit the epigenetic machinery in animal models is providing new insights into disease mechanisms in humans.

  13. Abnormal Fear Memory as a Model for Posttraumatic Stress Disorder.

    PubMed

    Desmedt, Aline; Marighetto, Aline; Piazza, Pier-Vincenzo

    2015-09-01

    For over a century, clinicians have consistently described the paradoxical co-existence in posttraumatic stress disorder (PTSD) of sensory intrusive hypermnesia and declarative amnesia for the same traumatic event. Although this amnesia is considered as a critical etiological factor of the development and/or persistence of PTSD, most current animal models in basic neuroscience have focused exclusively on the hypermnesia, i.e., the persistence of a strong fear memory, neglecting the qualitative alteration of fear memory. The latest is characterized by an underrepresentation of the trauma in the context-based declarative memory system in favor of its overrepresentation in a cue-based sensory/emotional memory system. Combining psychological and neurobiological data as well as theoretical hypotheses, this review supports the idea that contextual amnesia is at the core of PTSD and its persistence and that altered hippocampal-amygdalar interaction may contribute to such pathologic memory. In a first attempt to unveil the neurobiological alterations underlying PTSD-related hypermnesia/amnesia, we describe a recent animal model mimicking in mice some critical aspects of such abnormal fear memory. Finally, this line of argument emphasizes the pressing need for a systematic comparison between normal/adaptive versus abnormal/maladaptive fear memory to identify biomarkers of PTSD while distinguishing them from general stress-related, potentially adaptive, neurobiological alterations. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  14. Identification of Risk Factors for Chronic Posttraumatic Stress Disorder (PTSD)

    DTIC Science & Technology

    2008-07-01

    Disorder , 1% for Panic Disorder , 3% for Social Phobia, 1% for Obsessive Compulsive Disorder , 2% for Generalized Anxiety Disorder , 5% for Alcohol Abuse...Award Number: W81XWH-061-0573 TITLE: Identification of Risk Factors for Chronic Posttraumatic Stress Disorder (PTSD) PRINCIPAL INVESTIGATOR: M...CONTRACT NUMBER Identification of Risk Factors for Chronic Posttraumatic Stress Disorder (PTSD) 5b. GRANT NUMBER W81XWH-06-1-0573 5c. PROGRAM

  15. Catecholamines in Post-Traumatic Stress Disorder

    DTIC Science & Technology

    2012-07-01

    could lead to memories that are too strong, contributing to the recurrent, intrusive retrieval of the traumatic events that occurs in PTSD. As a...emotionally arousing experiences are typically vivid and persistent. The recurrent, intrusive memories of traumatic events in post-traumatic stress disorder...signaling plays a critical role in the maintenance of waking and in the regulation of REM sleep. J Neurophysiol 92:2071–2082. Ouyang M, Zhang L, Zhu

  16. Posttraumatic stress disorder: the missed diagnosis.

    PubMed

    Grasso, Damion; Boonsiri, Joseph; Lipschitz, Deborah; Guyer, Amanda; Houshyar, Shadi; Douglas-Palumberi, Heather; Massey, Johari; Kaufman, Joan

    2009-01-01

    Posttraumatic stress disorder (PTSD) is frequently underdiagnosed in maltreated samples. Protective services information is critical for obtaining complete trauma histories and determining whether to survey PTSD symptoms in maltreated children. In the current study, without protective services information to supplement parent and child report, diagnosing PTSD was missed in a significant proportion of the cases. Collaboration between mental health professionals and protective service workers is critical in determining psychiatric diagnoses and treatment needs of children involved with the child welfare system.

  17. The perioperative implications of posttraumatic stress disorder.

    PubMed

    Wofford, Ken; Hertzberg, Michael; Vacchiano, Charles

    2012-12-01

    Posttraumatic stress disorder (PTSD) is an anxiety disorder that develops after exposure to a traumatic event and is characterized by symptoms of reexperiencing, emotional numbing, persistent arousal, and avoidance. Approximately 6.8% of the people in the United States will be diagnosed with PTSD at some point in their lives. The presence of PTSD in a surgical patient can be important because PTSD is associated with the use of psychoactive medications, risky health behaviors, cardiovascular comorbidities, depression, chronic pain, and cognitive dysfunction, all of which may influence the risk of perioperative morbidity and mortality. In addition, patients with PTSD are anxious around unfamiliar people and in unfamiliar environments. The purposes of this journal course are to provide anesthetists with a working knowledge of the symptoms, treatments, and comorbidities associated with PTSD and to suggest ways of interacting with patients with the disorder that increase trust and decrease the risk of evoking posttraumatic symptoms in the perioperative environment.

  18. Posttraumatic stress disorder and cardiometabolic disease.

    PubMed

    Levine, Arlene Bradley; Levine, Lionel M; Levine, T Barry

    2014-01-01

    The need for addressing posttraumatic stress disorder (PTSD) among combat veterans returning from Afghanistan and Iraq is a growing public health concern. Current PTSD management addresses psychiatric parameters of this condition. However, PTSD is not simply a psychiatric disorder. Traumatic stress increases the risk for inflammation-related somatic diseases and early mortality. The metabolic syndrome reflects the increased health risk associated with combat stress and PTSD. Obesity, dyslipidemia, hypertension, diabetes mellitus, and cardiovascular disease are prevalent among PTSD patients. However, there has been little appreciation for the need to address these somatic PTSD comorbidities. Medical professionals treating this vulnerable population should screen patients for cardiometabolic risk factors and avail themselves of existing preventive diet, exercise, and pharmacologic modalities that will reduce such risk factors and improve overall long-term health outcomes and quality of life. There is the promise that cardiometabolic preventive therapy complementing psychiatric intervention may, in turn, help improve the posttraumatic stress system dysregulation and favorably impact psychiatric and neurologic function. © 2013 S. Karger AG, Basel.

  19. Central immune alterations in passive strategy following chronic defeat stress.

    PubMed

    Joana, Perez-Tejada; Amaia, Arregi; Arantza, Azpiroz; Garikoitz, Beitia; Eneritz, Gomez-Lazaro; Larraitz, Garmendia

    2016-02-01

    The relationship between stress, mood disorders and immune disorders is known, but what remains to be resolved is why certain individuals are more susceptible than others to suffer different disorders, along with the biological mechanisms that underlie these differences. The objective of this study was to analyze the changes in the expression patterns of proinflammatory cytokines in the hypothalamus, hippocampus, amygdala and prefrontal cortex after chronic defeat, depending on the coping strategy used. The expression levels of α1b and α2a adrenergic receptors and cytokine-inducible nitric oxide synthase (iNOS) in the prefrontal cortex were also measured. The results indicated that subjects with a passive coping strategy showed high levels of interleukin-6 (IL-6) and interleukin-1β (IL-1β) expression in several cerebral structures in resting conditions after 21 days of chronic stress and increases in these cytokine levels in the hippocampus following an additional stress. Low expression levels of tumour necrosis factor-alpha (TNF-α) in the prefrontal cortex in active subjects at rest and in passive subjects after an additional defeat were detected. The iNOS expression levels were lower in the prefrontal cortex of the active group at rest. With respect to adrenergic receptor expression, there were no changes as a function of stress, but there were changes as a function of coping strategy. These results indicate differences in the variables studied in terms of the coping strategy adopted, with passive subjects having a biological profile that could be considered more vulnerable to the development of stress-related disorders.

  20. The cortisol response to social stress in social anxiety disorder.

    PubMed

    Vaccarino, Oriana; Levitan, Robert; Ravindran, Arun

    2015-04-01

    This study evaluated the cortisol stress response (CSR) following the Trier Social Stress Test in Social Anxiety Disorder (SAD) and control participants, to determine whether individual differences in CSR associate more with SAD diagnosis or dimensional characteristics [i.e. childhood trauma (CT)]. Twenty-one participants (11 with SAD) had full data available for both CT-scores and cortisol area-under-the-curve (AUC). Linear regression produced significant results: predicting AUCG with study group, emotional abuse (EA) scores and their interaction (F=3.14, df=5,15; p=.039); of note, the study group by EA interaction was significant at p=.015, driven by a strong positive association between EA and cortisol AUCG in the control group, and a negative association between these variables in the SAD group (standardized-beta=1.56, t=2.75, p=.015). This suggests that EA in SAD patients is associated with altered CSR, highlighting need to measure dimensional characteristics.

  1. Neighborhood functions alter unbalanced facilitation on a stress gradient.

    PubMed

    Malanson, George P; Resler, Lynn M

    2015-01-21

    The stress-gradient hypothesis states that individual and species competitive and facilitative effects change in relative importance or intensity along environmental gradients of stress. The importance of the number of facilitators in the neighborhood of a potential beneficiary has not been explored. Evenly distributed and stress-correlated facilitation and the increase in the intensity of facilitation with neighbors as linear, logarithmic, and unimodal functions is simulated for two hypothetical species, both of which improve the local environment. The mutualism is unbalanced in that the establishment of one species is enhanced by neighbors more than the other. Compared to no facilitation or evenly distributed facilitation, the stress gradient produces more edges in the spatially advancing population, more overall intensity of facilitation, and more individuals further advanced into the area of higher stress; the more enhanced species has increased population relative to the other - to the point where they are equal. Among three neighborhood functions, little difference exists in outcomes between the linear and logarithmic functions, but the unimodal function, which shifts peak facilitation intensity to fewer neighbors, increases the above state variables more than the differences between the even and stress gradient facilitation scenarios; the population of the beneficiary species exceeds that of the other. Different neighborhood functions change the effects of spatial pattern on the biological outcome. The unbalanced mutualism may be important where additional species alter the basic interaction in the high stress area of the environmental gradient, such as ecotones where the spatial pattern becomes central to facilitation.

  2. Post-traumatic stress disorder and cancer.

    PubMed

    Cordova, Matthew J; Riba, Michelle B; Spiegel, David

    2017-04-01

    Being diagnosed with and treated for cancer is highly stressful and potentially traumatic. An extensive literature has evaluated the prevalence, predictors, and correlates of cancer-related post-traumatic stress disorder (PTSD) symptoms and diagnoses. In this qualitative review of cancer-related PTSD literature, we highlight conceptual, methodological, and diagnostic issues, and identify clinical implications and areas for future research. Cancer-related PTSD has been documented in a minority of patients with cancer and their family members, is positively associated with other indices of distress and reduced quality of life, and has several correlates and risk factors (eg, prior trauma history, pre-existing psychiatric conditions, poor social support). The literature on treatment of cancer-related PTSD is sparse. Existing literature on cancer-related PTSD has used DSM-IV-TR diagnostic criteria; the revised DSM-5 PTSD criteria have important implications for the assessment of cancer-related distress. Application of PTSD diagnosis to patients with cancer has been critiqued on conceptual and methodological grounds, and important differential diagnosis considerations should be taken into account. Psychosocial assessment of patients with cancer should include careful evaluation of pre-cancer diagnosis trauma and psychiatric history, and diagnostic interviewing should consider concurrent conditions (eg, adjustment disorder). Treatment of cancer-related PTSD should be approached with caution and be informed by existing evidence-based approaches for traumatic stress.

  3. Adulthood stress responses in rats are variably altered as a factor of adolescent stress exposure.

    PubMed

    Moore, Nicole L T; Altman, Daniel E; Gauchan, Sangeeta; Genovese, Raymond F

    2016-05-01

    Stress exposure during development may influence adulthood stress response severity. The present study investigates persisting effects of two adolescent stressors upon adulthood response to predator exposure (PE). Rats were exposed to underwater trauma (UWT) or PE during adolescence, then to PE after reaching adulthood. Rats were then exposed to predator odor (PO) to test responses to predator cues alone. Behavioral and neuroendocrine assessments were conducted to determine acute effects of each stress experience. Adolescent stress altered behavioral response to adulthood PE. Acoustic startle response was blunted. Bidirectional changes in plus maze exploration were revealed as a factor of adolescent stress type. Neuroendocrine response magnitude did not predict severity of adolescent or adult stress response, suggesting that different adolescent stress events may differentially alter developmental outcomes regardless of acute behavioral or neuroendocrine response. We report that exposure to two different stressors in adolescence may differentially affect stress response outcomes in adulthood. Acute response to an adolescent stressor may not be consistent across all stressors or all dependent measures, and may not predict alterations in developmental outcomes pertaining to adulthood stress exposure. Further studies are needed to characterize factors underlying long-term effects of a developmental stressor.

  4. Neuronal plasticity: a link between stress and mood disorders.

    PubMed

    Calabrese, Francesca; Molteni, Raffaella; Racagni, Giorgio; Riva, Marco A

    2009-12-01

    Although stress represents the major environmental element of susceptibility for mood disorders, the relationship between stress and disease remains to be fully established. In the present article we review the evidence in support for a role of neuronal plasticity, and in particular of neurotrophic factors. Even though decreased levels of norepinephrine and serotonin may underlie depressive symptoms, compelling evidence now suggests that mood disorders are characterized by reduced neuronal plasticity, which can be brought about by exposure to stress at different stages of life. Indeed the expression of neurotrophic molecules, such as the neurotrophin BDNF, is reduced in depressed subjects as well as in experimental animals exposed to adverse experience at early stages of life or at adulthood. These changes show an anatomical specificity and might be sustained by epigenetic mechanisms. Pharmacological intervention may normalize such defects and improve neuronal function through the modulation of the same factors that are defective in depression. Several studies have demonstrated that chronic, but not acute, antidepressant treatment increases the expression of BDNF and may enhance its localization at synaptic level. Antidepressant treatment can normalize deficits in neurotrophin expression produced by chronic stress paradigms, but may also alter the modulation of BDNF under acute stressful conditions. In summary, there is good agreement in considering neuronal plasticity, and the expression of key proteins such as the neurotrophin BDNF, as a central player for the effects of stress on brain function and its implication for psychopathology. Accordingly, effective treatments should not limit their effects to the control of neurotransmitter and hormonal dysfunctions, but should be able to normalize defective mechanisms that sustain the impairment of neuronal plasticity.

  5. Chronic mild stress alters circadian expressions of molecular clock genes in the liver.

    PubMed

    Takahashi, Kei; Yamada, Tetsuya; Tsukita, Sohei; Kaneko, Keizo; Shirai, Yuta; Munakata, Yuichiro; Ishigaki, Yasushi; Imai, Junta; Uno, Kenji; Hasegawa, Yutaka; Sawada, Shojiro; Oka, Yoshitomo; Katagiri, Hideki

    2013-02-01

    Chronic stress is well known to affect metabolic regulation. However, molecular mechanisms interconnecting stress response systems and metabolic regulations have yet to be elucidated. Various physiological processes, including glucose/lipid metabolism, are regulated by the circadian clock, and core clock gene dysregulation reportedly leads to metabolic disorders. Glucocorticoids, acting as end-effectors of the hypothalamus-pituitary-adrenal (HPA) axis, entrain the circadian rhythms of peripheral organs, including the liver, by phase-shifting core clock gene expressions. Therefore, we examined whether chronic stress affects circadian expressions of core clock genes and metabolism-related genes in the liver using the chronic mild stress (CMS) procedure. In BALB/c mice, CMS elevated and phase-shifted serum corticosterone levels, indicating overactivation of the HPA axis. The rhythmic expressions of core clock genes, e.g., Clock, Npas2, Bmal1, Per1, and Cry1, were altered in the liver while being completely preserved in the hypothalamic suprachiasmatic nuculeus (SCN), suggesting that the SCN is not involved in alterations in hepatic core clock gene expressions. In addition, circadian patterns of glucose and lipid metabolism-related genes, e.g., peroxisome proliferator activated receptor (Ppar) α, Pparγ-1, Pparγ-coactivator-1α, and phosphoenolepyruvate carboxykinase, were also disturbed by CMS. In contrast, in C57BL/6 mice, the same CMS procedure altered neither serum corticosterone levels nor rhythmic expressions of hepatic core clock genes and metabolism-related genes. Thus, chronic stress can interfere with the circadian expressions of both core clock genes and metabolism-related genes in the liver possibly involving HPA axis overactivation. This mechanism might contribute to metabolic disorders in stressful modern societies.

  6. Epigenetic and immune function profiles associated with posttraumatic stress disorder

    PubMed Central

    Uddin, Monica; Aiello, Allison E.; Wildman, Derek E.; Koenen, Karestan C.; Pawelec, Graham; de los Santos, Regina; Goldmann, Emily; Galea, Sandro

    2010-01-01

    The biologic underpinnings of posttraumatic stress disorder (PTSD) have not been fully elucidated. Previous work suggests that alterations in the immune system are characteristic of the disorder. Identifying the biologic mechanisms by which such alterations occur could provide fundamental insights into the etiology and treatment of PTSD. Here we identify specific epigenetic profiles underlying immune system changes associated with PTSD. Using blood samples (n = 100) obtained from an ongoing, prospective epidemiologic study in Detroit, the Detroit Neighborhood Health Study, we applied methylation microarrays to assay CpG sites from more than 14,000 genes among 23 PTSD-affected and 77 PTSD-unaffected individuals. We show that immune system functions are significantly overrepresented among the annotations associated with genes uniquely unmethylated among those with PTSD. We further demonstrate that genes whose methylation levels are significantly and negatively correlated with traumatic burden show a similar strong signal of immune function among the PTSD affected. The observed epigenetic variability in immune function by PTSD is corroborated using an independent biologic marker of immune response to infection, CMV—a typically latent herpesvirus whose activity was significantly higher among those with PTSD. This report of peripheral epigenomic and CMV profiles associated with mental illness suggests a biologic model of PTSD etiology in which an externally experienced traumatic event induces downstream alterations in immune function by reducing methylation levels of immune-related genes. PMID:20439746

  7. ELEVATED RISK FOR AUTOIMMUNE DISORDERS IN IRAQ AND AFGHANISTAN VETERANS WITH POSTTRAUMATIC STRESS DISORDER

    PubMed Central

    O’Donovan, Aoife; Cohen, Beth E.; Seal, Karen; Bertenthal, Dan; Margaretten, Mary; Nishimi, Kristen; Neylan, Thomas C.

    2014-01-01

    BACKGROUND Posttraumatic stress disorder (PTSD) is associated with endocrine and immune abnormalities that could increase risk for autoimmune disorders. However, little is known about the risk for autoimmune disorders among individuals with PTSD. METHODS We conducted a retrospective cohort study of 666,269 Iraq and Afghanistan veterans under age 55 who were enrolled in the Department of Veterans Affairs (VA) healthcare system between October 7, 2001 and March 31, 2011. Generalized linear models were used to examine if PTSD, other psychiatric disorders, and military sexual trauma exposure (MST) increase risk for autoimmune disorders, including thyroiditis, inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, and lupus erythematosus, adjusting for age, gender, race, and primary care visits. RESULTS PTSD was diagnosed in 203,766 (30.6%) veterans, and psychiatric disorders other than PTSD were diagnosed in an additional 129,704 (19.5%) veterans. Veterans diagnosed with PTSD had significantly higher adjusted relative risk (ARR) for diagnosis with any of the autoimmune disorders alone or in combination compared to veterans with no psychiatric diagnoses (ARR = 2.00, 95% CI, 1.91, 2.09), and compared to veterans diagnosed with psychiatric disorders other than PTSD (ARR = 1.51, 95% CI, 1.43, 1.59, p < .001). The magnitude of the PTSD-related increase in risk for autoimmune disorders was similar in women and men, and MST was independently associated with increased risk in both women and men. CONCLUSIONS Trauma exposure and PTSD may increase risk for autoimmune disorders. Altered immune function, lifestyle factors, or shared etiology may underlie this association. PMID:25104173

  8. Elevated risk for autoimmune disorders in iraq and afghanistan veterans with posttraumatic stress disorder.

    PubMed

    O'Donovan, Aoife; Cohen, Beth E; Seal, Karen H; Bertenthal, Dan; Margaretten, Mary; Nishimi, Kristen; Neylan, Thomas C

    2015-02-15

    Posttraumatic stress disorder (PTSD) is associated with endocrine and immune abnormalities that could increase risk for autoimmune disorders. However, little is known about the risk for autoimmune disorders among individuals with PTSD. We conducted a retrospective cohort study of 666,269 Iraq and Afghanistan veterans under age 55 who were enrolled in the Department of Veterans Affairs health care system between October 7, 2001, and March 31, 2011. Generalized linear models were used to examine if PTSD, other psychiatric disorders, and military sexual trauma exposure increased risk for autoimmune disorders, including thyroiditis, inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, and lupus erythematosus, adjusting for age, gender, race, and primary care visits. PTSD was diagnosed in 203,766 veterans (30.6%), and psychiatric disorders other than PTSD were diagnosed in an additional 129,704 veterans (19.5%). Veterans diagnosed with PTSD had significantly higher adjusted relative risk (ARR) for diagnosis with any of the autoimmune disorders alone or in combination compared with veterans with no psychiatric diagnoses (ARR = 2.00; 95% confidence interval, 1.91-2.09) and compared with veterans diagnosed with psychiatric disorders other than PTSD (ARR = 1.51; 95% confidence interval, 1.43-1.59; p < .001). The magnitude of the PTSD-related increase in risk for autoimmune disorders was similar in women and men, and military sexual trauma exposure was independently associated with increased risk in both women and men. Trauma exposure and PTSD may increase risk for autoimmune disorders. Altered immune function, lifestyle factors, or shared etiology may underlie this association. Copyright © 2015 Society of Biological Psychiatry. All rights reserved.

  9. Cannabinoids prevent the development of behavioral and endocrine alterations in a rat model of intense stress.

    PubMed

    Ganon-Elazar, Eti; Akirav, Irit

    2012-01-01

    Cannabinoids have recently emerged as a possible treatment of stress- and anxiety-related disorders such as post-traumatic stress disorder (PTSD). Here, we examined whether cannabinoid receptor activation could prevent the effects of traumatic stress on the development of behavioral and neuroendocrine measures in a rat model of PTSD, the single-prolonged stress (SPS) model. Rats were injected with the CB1/CB2 receptor agonist WIN55,212-2 (WIN) systemically or into the basolateral amygdala (BLA) at different time points following SPS exposure and were tested 1 week later for inhibitory avoidance (IA) conditioning and extinction, acoustic startle response (ASR), hypothalamic-pituitary-adrenal (HPA) axis function, and anxiety levels. Exposure to SPS enhanced conditioned avoidance and impaired extinction while enhancing ASR, negative feedback on the HPA axis, and anxiety. WIN (0.5 mg/kg) administered intraperitoneally 2 or 24 h (but not 48 h) after SPS prevented the trauma-induced alterations in IA conditioning and extinction, ASR potentiation, and HPA axis inhibition. WIN microinjected into the BLA (5 μg/side) prevented SPS-induced alterations in IA and ASR. These effects were blocked by intra-BLA co-administration of the CB1 receptor antagonist AM251 (0.3 ng/side), suggesting the involvement of CB1 receptors. These findings suggest that (i) there may be an optimal time window for intervention treatment with cannabinoids after exposure to a highly stressful event, (ii) some of the preventive effects induced by WIN are mediated by an activation of CB1 receptors in the BLA, and (iii) cannabinoids could serve as a pharmacological treatment of stress- and trauma-related disorders.

  10. Cannabinoids Prevent the Development of Behavioral and Endocrine Alterations in a Rat Model of Intense Stress

    PubMed Central

    Ganon-Elazar, Eti; Akirav, Irit

    2012-01-01

    Cannabinoids have recently emerged as a possible treatment of stress- and anxiety-related disorders such as post-traumatic stress disorder (PTSD). Here, we examined whether cannabinoid receptor activation could prevent the effects of traumatic stress on the development of behavioral and neuroendocrine measures in a rat model of PTSD, the single-prolonged stress (SPS) model. Rats were injected with the CB1/CB2 receptor agonist WIN55,212-2 (WIN) systemically or into the basolateral amygdala (BLA) at different time points following SPS exposure and were tested 1 week later for inhibitory avoidance (IA) conditioning and extinction, acoustic startle response (ASR), hypothalamic-pituitary-adrenal (HPA) axis function, and anxiety levels. Exposure to SPS enhanced conditioned avoidance and impaired extinction while enhancing ASR, negative feedback on the HPA axis, and anxiety. WIN (0.5 mg/kg) administered intraperitoneally 2 or 24 h (but not 48 h) after SPS prevented the trauma-induced alterations in IA conditioning and extinction, ASR potentiation, and HPA axis inhibition. WIN microinjected into the BLA (5 μg/side) prevented SPS-induced alterations in IA and ASR. These effects were blocked by intra-BLA co-administration of the CB1 receptor antagonist AM251 (0.3 ng/side), suggesting the involvement of CB1 receptors. These findings suggest that (i) there may be an optimal time window for intervention treatment with cannabinoids after exposure to a highly stressful event, (ii) some of the preventive effects induced by WIN are mediated by an activation of CB1 receptors in the BLA, and (iii) cannabinoids could serve as a pharmacological treatment of stress- and trauma-related disorders. PMID:21918506

  11. Initial transference of wild birds to captivity alters stress physiology.

    PubMed

    Dickens, Molly J; Earle, Kristen A; Romero, L Michael

    2009-01-01

    Maintaining wild animals in captivity has long been used for conservation and research. While often suggested that captivity causes chronic stress, impacts on the underlying stress physiology are poorly understood. We used wild-caught chukar (Alectoris chukar) as a model avian species to assess how the initial 10 days of captivity alters the corticosterone (CORT) secretory pathway. In the first few days of captivity, birds lost weight, had lower hematocrit and demonstrated changes in CORT concentrations. Both baseline and restraint-stress-induced CORT concentrations decreased by days 3-5 of captivity and remained significantly lower throughout the 10 days although stress-induced concentrations began to recover by day 9. To delineate potential mechanisms underlying these CORT changes, we evaluated alterations to the hypothalamic-pituitary-adrenal (HPA) axis. Although chukar appear to be resistant to arginine vasotocin's (AVT) effects on CORT release, adrenocorticotropin hormone (ACTH) stimulated CORT release; however, ACTH stimulation did not differ during the 10 days of captivity. In contrast, negative feedback axis sensitivity, as determined by both dexamethasone suppression as well as endogenous negative feedback, decreased by day 5 but was regained by day 9. In addition, the combined stressors of capture and long distance transport eliminated the animals' ability to mount an acute CORT response on the day following the move. Therefore, introduction into captivity appeared to shift the chukar into a temporary state of chronic stress that began to recover within 9days. The duration of these alterations likely varies due to differences in capture techniques, transport distance, and species studied.

  12. Altered locus coeruleus-norepinephrine function following single prolonged stress.

    PubMed

    George, Sophie A; Knox, Dayan; Curtis, Andre L; Aldridge, J Wayne; Valentino, Rita J; Liberzon, Israel

    2013-03-01

    Data from preclinical and clinical studies have implicated the norepinephrine system in the development and maintenance of post-traumatic stress disorder. The primary source of norepinephrine in the forebrain is the locus coeruleus (LC); however, LC activity cannot be directly measured in humans, and previous research has often relied upon peripheral measures of norepinephrine to infer changes in central LC-norepinephrine function. To directly assess LC-norepinephrine function, we measured single-unit activity of LC neurons in a validated rat model of post-traumatic stress disorder - single prolonged stress (SPS). We also examined tyrosine hydroxylase mRNA levels in the LC of SPS and control rats as an index of norepinephrine utilisation. For electrophysiological recordings, 92 LC neurons were identified from 19 rats (SPS, 12; control, 7), and spontaneous and evoked responses to a noxious event (paw compression) were recorded. Baseline and restraint stress-evoked tyrosine hydroxylase mRNA expression levels were measured in SPS and control rats (n = 16 per group) in a separate experiment. SPS rats showed lower spontaneous activity but higher evoked responses, leading to an enhanced signal-to-noise ratio of LC neurons, accompanied by impaired recovery from post-stimulus inhibition. In concert, tyrosine hydroxylase mRNA expression in the LC of SPS rats tended to be lower at baseline, but was exaggerated following restraint stress. These data demonstrate persistent changes in LC function following stress/trauma in a rat model of post-traumatic stress, as measured by differences in both the electrophysiological properties of LC neurons and tyrosine hydroxylase mRNA transcription.

  13. Biological Studies of Posttraumatic Stress Disorder

    PubMed Central

    Pitman, Roger K.; Rasmusson, Ann M.; Koenen, Karestan C.; Shin, Lisa M.; Orr, Scott P.; Gilbertson, Mark W.; Milad, Mohammed R.; Liberzon, Israel

    2016-01-01

    Preface Posttraumatic stress disorder (PTSD) is the only major mental disorder for which a cause is considered to be known, viz., an event that involves threat to the physical integrity of oneself or others and induces a response of intense fear, helplessness, or horror. Although PTSD is still largely regarded as a psychological phenomenon, over the past three decades the growth of the biological PTSD literature has been explosive, and thousands of references now exist. Ultimately, the impact of an environmental event, such as a psychological trauma, must be understood at organic, cellular, and molecular levels. The present review attempts to present the current state of this understanding, based upon psychophysiological, structural and functional neuroimaging, endocrinological, genetic, and molecular biological studies in humans and in animal models. PMID:23047775

  14. DSM-5 and posttraumatic stress disorder.

    PubMed

    Levin, Andrew P; Kleinman, Stuart B; Adler, John S

    2014-01-01

    The latest iteration of the posttraumatic stress disorder (PTSD) criteria presented in The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) includes specific elaborations of the gatekeeper criteria, a new category of stressor, an expansion in the number of symptoms, addition of a new subtype of PTSD, and an enlarged text discussion that breaks new ground in defining the criteria. We first trace the rationale underlying these changes and their impact on the prevalence of PTSD diagnoses in clinical studies and then present potential implications of the new criteria for forensic assessment methodology and the detection of malingering, interpretations of criminal responsibility and mitigation, evaluation of the reliability of witnesses, the scope of claims in civil and employment cases, and eligibility for disability. © 2014 American Academy of Psychiatry and the Law.

  15. Altered default mode network functional connectivity in schizotypal personality disorder.

    PubMed

    Zhang, Qing; Shen, Jing; Wu, Jianlin; Yu, Xiao; Lou, Wutao; Fan, Hongyu; Shi, Lin; Wang, Defeng

    2014-12-01

    The default mode network (DMN) has been identified to play a critical role in many mental disorders, but such abnormalities have not yet been determined in patients with schizotypal personality disorder (SPD). The purpose of this study was to analyze the alteration of the DMN functional connectivity in subjects with (SPD) and compared it to healthy control subjects. Eighteen DSM-IV diagnosed SPD subjects (all male, average age: 19.7±0.9) from a pool of 3000 first year college students, and eighteen age and gender matched healthy control subjects were recruited (all male, average age: 20.3±0.9). Independent component analysis (ICA) was used to analyze the DMN functional connectivity alteration. Compared to the healthy control group, SPD subjects had significantly decreased functional connectivity in the frontal areas, including the superior and medial frontal gyrus, and greater functional connectivity in the bilateral superior temporal gyrus and sub-lobar regions, including the bilateral putamen and caudate. Compared to subjects with SPD, the healthy control group showed decreased functional connectivity in the bilateral posterior cingulate gyrus, but showed greater functional connectivity in the right transverse temporal gyrus and left middle temporal gyrus. The healthy control group also showed greater activation in the cerebellum compared to the SPD group. These findings suggest that DMN functional connectivity, particularly that involving cognitive or emotional regulation, is altered in SPD subjects, and thus may be helpful in studying schizophrenia.

  16. Awareness of identity alteration and diagnostic preference between borderline personality disorder and dissociative disorders.

    PubMed

    Sar, Vedat; Alioğlu, Firdevs; Akyuz, Gamze; Tayakısı, Emre; Öğülmüş, Ezgi F; Sönmez, Doğuş

    2017-01-01

    This study inquires into identity alteration among college students and its relationship to borderline personality disorder (BPD) and/or dissociative disorders (DDs). Steinberg Identity Alteration Questionnaire (SIAQ), Childhood Trauma Questionnaire (CTQ), and self-report screening tool of the BPD section of the Structured Clinical Interview for DSM-IV (SCID-BPD) were administered to 1301 college students. Participants who fit the diagnostic criteria of BPD (n = 80) according to the clinician-administered SCID-BPD and 111 non-BPD controls were evaluated using the Structured Clinical Interview for DSM-IV DDs (SCID-D) by two psychiatrists blind to the group membership and scale scores. Test-retest evaluations and internal consistency analyses suggested that SIAQ was a reliable instrument. Of the participants, 11.3% reported a SIAQ score 25 or above alongside some impairment. SIAQ scores differentiated participants who fit the diagnostic criteria for a DD from those who did not. While self-report identity alteration was correlated with all childhood trauma types, clinician-assessed identity alteration was correlated with childhood sexual abuse only. Those who fit criteria for both disorders had the highest identity alteration scores in self-report and clinician-assessment. Although both syndromes had significant effect on self-report identity alteration total scores, in contrast to DD, BPD did not have an effect on the clinician-administered evaluation. An impression of personality disorder rather than a DD may seem more likely when identity alteration remains subtle in clinical assessment, notwithstanding its presence in self-report. Lack of recognition of identity alteration may lead to overdiagnosis of BPD among individuals who have a DD.

  17. Osmotic stress alters chromatin condensation and nucleocytoplasmic transport

    SciTech Connect

    Finan, John D.; Leddy, Holly A.; Guilak, Farshid

    2011-05-06

    Highlights: {yields} The rate of nucleocytoplasmic transport increases under hyper-osmotic stress. {yields} The mechanism is a change in nuclear geometry, not a change in permeability of the nuclear envelope. {yields} Intracytoplasmic but not intranuclear diffusion is sensitive to osmotic stress. {yields} Pores in the chromatin of the nucleus enlarge under hyper-osmotic stress. -- Abstract: Osmotic stress is a potent regulator of biological function in many cell types, but its mechanism of action is only partially understood. In this study, we examined whether changes in extracellular osmolality can alter chromatin condensation and the rate of nucleocytoplasmic transport, as potential mechanisms by which osmotic stress can act. Transport of 10 kDa dextran was measured both within and between the nucleus and the cytoplasm using two different photobleaching methods. A mathematical model was developed to describe fluorescence recovery via nucleocytoplasmic transport. As osmolality increased, the diffusion coefficient of dextran decreased in the cytoplasm, but not the nucleus. Hyper-osmotic stress decreased nuclear size and increased nuclear lacunarity, indicating that while the nucleus was getting smaller, the pores and channels interdigitating the chromatin had expanded. The rate of nucleocytoplasmic transport was increased under hyper-osmotic stress but was insensitive to hypo-osmotic stress, consistent with the nonlinear osmotic properties of the nucleus. The mechanism of this osmotic sensitivity appears to be a change in the size and geometry of the nucleus, resulting in a shorter effective diffusion distance for the nucleus. These results may explain physical mechanisms by which osmotic stress can influence intracellular signaling pathways that rely on nucleocytoplasmic transport.

  18. The association of posttraumatic stress disorder, complex posttraumatic stress disorder, and borderline personality disorder from a network analytical perspective.

    PubMed

    Knefel, Matthias; Tran, Ulrich S; Lueger-Schuster, Brigitte

    2016-10-01

    Posttraumatic Stress Disorder (PTSD), Complex PTSD, and Borderline Personality Disorder (BPD) share etiological risk factors and an overlapping set of associated symptoms. Since the ICD-11 proposal for trauma-related disorders, the relationship of these disorders has to be clarified. A novel approach to psychopathology, network analysis, allows for a detailed analysis of comorbidity on symptom level. Symptoms were assessed in adult survivors of childhood abuse (N=219) using the newly developed ICD-11 Trauma-Questionnaire and the SCID-II. The psychopathological network was analyzed using the network approach. PTSD and Complex PTSD symptoms were strongly connected within disorders and to a lesser degree between disorders. Symptoms of BPD were weakly connected to others. Re-experiencing and dissociation were the most central symptoms. Mental disorders are no discrete entities, clear boundaries are unlikely to be found. The psychopathological network revealed central symptoms that might be important targets for specific first interventions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. FKBP5 polymorphisms influence pre-learning stress-induced alterations of learning and memory.

    PubMed

    Zoladz, Phillip R; Dailey, Alison M; Nagle, Hannah E; Fiely, Miranda K; Mosley, Brianne E; Brown, Callie M; Duffy, Tessa J; Scharf, Amanda R; Earley, McKenna B; Rorabaugh, Boyd R

    2017-03-01

    FK506 binding protein 51 (FKBP5) is a co-chaperone of heat shock protein 90 and significantly influences glucocorticoid receptor sensitivity. Single nucleotide polymorphisms (SNPs) in the FKBP5 gene are associated with altered hypothalamus-pituitary-adrenal (HPA) axis function, changes in the structure and function of several cognitive brain areas, and increased susceptibility to post-traumatic stress disorder, major depression, bipolar disorder and suicidal events. The mechanisms underlying these associations are largely unknown, but it has been speculated that the influence of these SNPs on emotional memory systems may play a role. In the present study, 112 participants were exposed to the socially evaluated cold pressor test (stress) or control (no stress) conditions immediately prior to learning a list of 42 words. Participant memory was assessed immediately after learning (free recall) and 24 h later (free recall and recognition). Participants provided a saliva sample that enabled the genotyping of three FKBP5 polymorphisms: rs1360780, rs3800373 and rs9296158. Results showed that stress impaired immediate recall in risk allele carriers. More importantly, stress enhanced long-term recall and recognition memory in non-carriers of the risk alleles, effects that were completely absent in risk allele carriers. Follow-up analyses revealed that memory performance was correlated with salivary cortisol levels in non-carriers, but not in carriers. These findings suggest that FKBP5 risk allele carriers may possess a sensitized stress response system, perhaps specifically for stress-induced changes in corticosteroid levels, which might aid our understanding of how SNPs in the FKBP5 gene confer increased risk for stress-related psychological disorders and their related phenotypes.

  20. Osmotic stress alters chromatin condensation and nucleocytoplasmic transport

    PubMed Central

    Finan, John D.; Leddy, Holly A.; Guilak, Farshid

    2011-01-01

    Osmotic stress is a potent regulator of biological function in many cell types, but its mechanism of action is only partially understood. In this study, we examined whether changes in extracellular osmolality can alter chromatin condensation and the rate of nucleocytoplasmic transport, as potential mechanisms by which osmotic stress can act. Transport of 10 kDa dextran was measured both within and between the nucleus and the cytoplasm using two different photobleaching methods. A mathematical model was developed to describe fluorescence recovery via nucleocytoplasmic transport. As osmolality increased, the diffusion coefficient of dextran decreased in the cytoplasm, but not the nucleus. Hyper-osmotic stress decreased nuclear size and increased nuclear lacunarity, indicating that while the nucleus was getting smaller, the pores and channels interdigitating the chromatin had expanded. The rate of nucleocytoplasmic transport was increased under hyper-osmotic stress but was insensitive to hypo-osmotic stress, consistent with the nonlinear osmotic properties of the nucleus. The mechanism of this osmotic sensitivity appears to be a change in the size and geometry of the nucleus, resulting in a shorter effective diffusion distance for the nucleus. These results may explain physical mechanisms by which osmotic stress can influence intracellular signaling pathways that rely on nucleocytoplasmic transport. PMID:21463604

  1. Alteration of Golgi Structure by Stress: A Link to Neurodegeneration?

    PubMed Central

    Alvarez-Miranda, Eduardo A.; Sinnl, Markus; Farhan, Hesso

    2015-01-01

    The Golgi apparatus is well-known for its role as a sorting station in the secretory pathway as well as for its role in regulating post-translational protein modification. Another role for the Golgi is the regulation of cellular signaling by spatially regulating kinases, phosphatases, and GTPases. All these roles make it clear that the Golgi is a central regulator of cellular homeostasis. The response to stress and the initiation of adaptive responses to cope with it are fundamental abilities of all living cells. It was shown previously that the Golgi undergoes structural rearrangements under various stress conditions such as oxidative or osmotic stress. Neurodegenerative diseases are also frequently associated with alterations of Golgi morphology and many stress factors have been described to play an etiopathological role in neurodegeneration. It is however unclear whether the stress-Golgi connection plays a role in neurodegenerative diseases. Using a combination of bioinformatics modeling and literature mining, we will investigate evidence for such a tripartite link and we ask whether stress-induced Golgi arrangements are cause or consequence in neurodegeneration. PMID:26617486

  2. Benefits of agomelatine in behavioral, neurochemical and blood brain barrier alterations in prenatal valproic acid induced autism spectrum disorder.

    PubMed

    Kumar, Hariom; Sharma, B M; Sharma, Bhupesh

    2015-12-01

    Valproic acid administration during gestational period causes behavior and biochemical deficits similar to those observed in humans with autism spectrum disorder. Although worldwide prevalence of autism spectrum disorder has been increased continuously, therapeutic agents to ameliorate the social impairment are very limited. The present study has been structured to investigate the therapeutic potential of melatonin receptor agonist, agomelatine in prenatal valproic acid (Pre-VPA) induced autism spectrum disorder in animals. Pre-VPA has produced reduction in social interaction (three chamber social behavior apparatus), spontaneous alteration (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complex I, II, IV). Furthermore, Pre-VPA has increased locomotor activity (actophotometer), anxiety, brain oxidative stress (thiobarbituric acid reactive species, glutathione, and catalase), nitrosative stress (nitrite/nitrate), inflammation (brain and ileum myeloperoxidase activity), calcium levels and blood brain barrier leakage in animals. Treatment with agomelatine has significantly attenuated Pre-VPA induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, agomelatine also attenuated Pre-VPA induced increase in locomotion, anxiety, brain oxidative stress, nitrosative stress, inflammation, calcium levels and blood brain barrier leakage. It is concluded that, Pre-VPA has induced autism spectrum disorder, which was attenuated by agomelatine. Agomelatine has shown ameliorative effect on behavioral, neurochemical and blood brain barrier alteration in Pre-VPA exposed animals. Thus melatonin receptor agonists may provide beneficial therapeutic strategy for managing autism spectrum disorder.

  3. Prenatal stress-induced alterations in major physiological systems correlate with gut microbiota composition in adulthood.

    PubMed

    Golubeva, Anna V; Crampton, Sean; Desbonnet, Lieve; Edge, Deirdre; O'Sullivan, Orla; Lomasney, Kevin W; Zhdanov, Alexander V; Crispie, Fiona; Moloney, Rachel D; Borre, Yuliya E; Cotter, Paul D; Hyland, Niall P; O'Halloran, Ken D; Dinan, Timothy G; O'Keeffe, Gerard W; Cryan, John F

    2015-10-01

    Early-life adverse experiences, including prenatal stress (PNS), are associated with a higher prevalence of neurodevelopmental, cardiovascular and metabolic disorders in affected offspring. Here, in a rat model of chronic PNS, we investigate the impact of late gestational stress on physiological outcomes in adulthood. Sprague-Dawley pregnant dams were subjected to repeated restraint stress from embryonic day 14 to day 20, and their male offspring were assessed at 4 months of age. PNS induced an exaggeration of the hypothalamic-pituitary-adrenal (HPA) axis response to stress, as well as an elevation of blood pressure and impairment of cognitive function. Altered respiratory control was also observed, as demonstrated by increased variability in basal respiratory frequency and abnormal frequency responses to both hypoxic and hypercapnic challenges. PNS also affected gastrointestinal neurodevelopment and function, as measured by a decrease in the innervation density of distal colon and an increase in the colonic secretory response to catecholaminergic stimulation. Finally, PNS induced long lasting alterations in the intestinal microbiota composition. 16S rRNA gene 454 pyrosequencing revealed a strong trend towards decreased numbers of bacteria in the Lactobacillus genus, accompanied by elevated abundance of the Oscillibacter, Anaerotruncus and Peptococcus genera in PNS animals. Strikingly, relative abundance of distinct bacteria genera significantly correlated with certain respiratory parameters and the responsiveness of the HPA axis to stress. Together, these findings provide novel evidence that PNS induces long-term maladaptive alterations in the gastrointestinal and respiratory systems, accompanied by hyper-responsiveness to stress and alterations in the gut microbiota. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Hormonal contraception use alters stress responses and emotional memory.

    PubMed

    Nielsen, Shawn E; Segal, Sabrina K; Worden, Ian V; Yim, Ilona S; Cahill, Larry

    2013-02-01

    Emotionally arousing material is typically better remembered than neutral material. Since norepinephrine and cortisol interact to modulate emotional memory, sex-related influences on stress responses may be related to sex differences in emotional memory. Two groups of healthy women - one naturally cycling (NC women, n=42) and one using hormonal contraceptives (HC women, n=36) - viewed emotionally arousing and neutral images. Immediately after, they were assigned to Cold Pressor Stress (CPS) or a control procedure. One week later, participants received a surprise free recall test. Saliva samples were collected and later assayed for salivary alpha-amylase (biomarker for norepinephrine) and cortisol. Compared to NC women, HC women exhibited significantly blunted stress hormone responses to the images and CPS. Recall of emotional images differed between HC and NC women depending on noradrenergic and cortisol responses. These findings may have important implications for understanding the neurobiology of emotional memory disorders, especially those that disproportionately affect women.

  5. Effect of Hemin on Brain Alterations and Neuroglobin Expression in Water Immersion Restraint Stressed Rats

    PubMed Central

    Ragy, Merhan; Ali, Fatma; Ramzy, Maggie M.

    2016-01-01

    In the brain, the heme oxygenase (HO) system has been reported to be very active and its modulation seems to play a crucial role in the pathophysiology of neurodegenerative disorders. Hemin as HO-1 inducer has been shown to attenuate neuronal injury so the goal of this study was to assess the effect of hemin therapy on the acute stress and how it would modulate neurological outcome. Thirty male albino rats were divided into three groups: control group and stressed group with six-hour water immersion restraint stress (WIRS) and stressed group, treated with hemin, in which each rat received a single intraperitoneal injection of hemin at a dose level of 50 mg/kg body weight at 12 hours before exposure to WIRS. Stress hormones, oxidative stress markers, malondialdehyde (MDA), and total antioxidant capacity (TAC) were measured and expressions of neuroglobin and S100B mRNA in brain tissue were assayed. Our results revealed that hemin significantly affects brain alterations induced by acute stress and this may be through increased expression of neuroglobin and through antioxidant effect. Hemin decreased blood-brain barrier damage as it significantly decreased the expression of S100B. These results suggest that hemin may be an effective therapy for being neuroprotective against acute stress. PMID:27073715

  6. Rifaximin Alters Intestinal Bacteria and Prevents Stress-Induced Gut Inflammation and Visceral Hyperalgesia in Rats

    PubMed Central

    Xu, Dabo; Gao, Jun; Gillilland, Merritt; Wu, Xiaoyin; Song, Il; Kao, John Y.; Owyang, Chung

    2014-01-01

    Background & Aims Rifaximin is used to treat patients with functional gastrointestinal disorders, but little is known about its therapeutic mechanism. We propose that rifaximin modulates the ileal bacterial community, reduces subclinical inflammation of the intestinal mucosa, and improves gut barrier function to reduce visceral hypersensitivity. Methods We induced visceral hyperalgesia in rats, via chronic water avoidance or repeat restraint stressors, and investigated whether rifaximin altered the gut microbiota, prevented intestinal inflammation, and improved gut barrier function. Quantitative polymerase chain reaction and 454 pyrosequencing were used to analyze bacterial 16S rRNA in ileal contents from the rats. Reverse transcription, immunoblot, and histologic analyses were used to evaluate levels of cytokines, the tight junction protein occludin, and mucosal inflammation, respectively. Intestinal permeability and rectal sensitivity were measured. Results Water avoidance and repeat restraint stress each led to visceral hyperalgesia, accompanied by mucosal inflammation and impaired mucosal barrier function. Oral rifaximin altered the composition of bacterial communities in the ileum (Lactobacillus species became the most abundant) and prevented mucosal inflammation, impairment to intestinal barrier function, and visceral hyperalgesia in response to chronic stress. Neomycin also changed the composition of the ileal bacterial community (Proteobacteria became the most abundant species). Neomycin did not prevent intestinal inflammation or induction of visceral hyperalgesia induced by water avoidance stress. Conclusions Rifaximin alters the bacterial population in the ileum of rats, leading to a relative abundance of Lactobacillus. These changes prevent intestinal abnormalities and visceral hyperalgesia in response to chronic psychological stress. PMID:24161699

  7. Rifaximin alters intestinal bacteria and prevents stress-induced gut inflammation and visceral hyperalgesia in rats.

    PubMed

    Xu, Dabo; Gao, Jun; Gillilland, Merritt; Wu, Xiaoyin; Song, Il; Kao, John Y; Owyang, Chung

    2014-02-01

    Rifaximin is used to treat patients with functional gastrointestinal disorders, but little is known about its therapeutic mechanism. We propose that rifaximin modulates the ileal bacterial community, reduces subclinical inflammation of the intestinal mucosa, and improves gut barrier function to reduce visceral hypersensitivity. We induced visceral hyperalgesia in rats, via chronic water avoidance or repeat restraint stressors, and investigated whether rifaximin altered the gut microbiota, prevented intestinal inflammation, and improved gut barrier function. Quantitative polymerase chain reaction (PCR) and 454 pyrosequencing were used to analyze bacterial 16S ribosomal RNA in ileal contents from the rats. Reverse transcription, immunoblot, and histologic analyses were used to evaluate levels of cytokines, the tight junction protein occludin, and mucosal inflammation, respectively. Intestinal permeability and rectal sensitivity were measured. Water avoidance and repeat restraint stress each led to visceral hyperalgesia, accompanied by mucosal inflammation and impaired mucosal barrier function. Oral rifaximin altered the composition of bacterial communities in the ileum (Lactobacillus species became the most abundant) and prevented mucosal inflammation, impairment to intestinal barrier function, and visceral hyperalgesia in response to chronic stress. Neomycin also changed the composition of the ileal bacterial community (Proteobacteria became the most abundant species). Neomycin did not prevent intestinal inflammation or induction of visceral hyperalgesia induced by water avoidance stress. Rifaximin alters the bacterial population in the ileum of rats, leading to a relative abundance of Lactobacillus. These changes prevent intestinal abnormalities and visceral hyperalgesia in response to chronic psychological stress. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  8. Antenatal Maternal Stress Alters Functional Brain Responses In Adult Offspring During Conditioned Fear

    PubMed Central

    Sadler, Theodore R.; Nguyen, Peter T.; Yang, Jun; Givrad, Tina K.; Mayer, Emeran A.; Maarek, Jean-Michel I.; Hinton, David R.; Holschneider, Daniel P.

    2011-01-01

    Antenatal maternal stress has been shown in rodent models and in humans to result in altered behavioral and neuroendocrine responses, yet little is known about its effects on functional brain activation. Pregnant female rats received a daily foot-shock stress or sham-stress two days after testing plug-positive and continuing for the duration of their pregnancy. Adult male offspring (age 14 weeks) with and without prior maternal stress (MS) were exposed to an auditory fear conditioning (CF) paradigm. Cerebral blood flow (CBF) was assessed during recall of the tone cue in the nonsedated, nontethered animal using the 14C-iodoantipyrine method, in which the tracer was administered intravenously by remote activation of an implantable minipump. Regional CBF distribution was examined by autoradiography and analyzed by statistical parametric mapping in the three-dimensionally reconstructed brains. Presence of fear memory was confirmed by behavioral immobility (‘freezing’). Corticosterone plasma levels during the CF paradigm were measured by ELISA in a separate group of rats. Antenatal MS exposure altered functional brain responses to the fear conditioned cue in adult offspring. Rats with prior MS exposure compared to those without demonstrated heightened fear responsivity, exaggerated and prolonged corticosterone release, increased functional cerebral activation of limbic/paralimbic regions (amygdala, ventral hippocampus, insula, ventral striatum, nucleus acumbens), the locus coeruleus, and white matter, and deactivation of medial prefrontal cortical regions. Dysregulation of corticolimbic circuits may represent risk factors in the future development of anxiety disorders and associated alterations in emotional regulation. PMID:21300034

  9. Restraint stress alters neutrophil and macrophage phenotypes during wound healing

    PubMed Central

    Tymen, Stéphanie D.; Rojas, Isolde G.; Zhou, Xiaofeng; Fang, Zong Juan; Zhao, Yan; Marucha, Phillip T.

    2013-01-01

    Previous studies reported that stress delays wound healing, impairs bacterial clearance, and elevates the risk for opportunistic infection. Neutrophils and macrophages are responsible for the removal of bacteria present at the wound site. The appropriate recruitment and functions of these cells are necessary for efficient bacterial clearance. In our current study we found that restraint stress induced an excessive recruitment of neutrophils extending the inflammatory phase of healing, and the gene expression of neutrophil attracting chemokines MIP-2 and KC. However, restraint stress did not affect macrophage infiltration. Stress decreased the phagocytic abilities of phagocytic cells ex vivo, yet it did not affect superoxide production. The cell surface expression of adhesion molecules CD11b and TLR4 were decreased in peripheral blood monocytes in stressed mice. The phenotype of macrophages present at the wound site was also altered. Gene expression of markers of pro-inflammatory classically activated macrophages, CXCL10 and CCL5, were down-regulated; as were markers associated with wound healing macrophages, CCL22, IGF-1, RELMα; and the regulatory macrophage marker, chemokine CCL1. Restraint stress also induced up-regulation of IL10 gene expression. In summary, our study has shown that restraint stress suppresses the phenotype shift of the macrophage population, as compared to the changes observed during normal wound healing, while the number of macrophages remains constant. We also observed a general suppression of chemokine gene expression. Modulation of the macrophage phenotype could provide a new therapeutic approach in the treatment of wounds under stress conditions in the clinical setting. PMID:22884902

  10. Restraint stress alters neutrophil and macrophage phenotypes during wound healing.

    PubMed

    Tymen, Stéphanie D; Rojas, Isolde G; Zhou, Xiaofeng; Fang, Zong Juan; Zhao, Yan; Marucha, Phillip T

    2013-02-01

    Previous studies reported that stress delays wound healing, impairs bacterial clearance, and elevates the risk for opportunistic infection. Neutrophils and macrophages are responsible for the removal of bacteria present at the wound site. The appropriate recruitment and functions of these cells are necessary for efficient bacterial clearance. In our current study we found that restraint stress induced an excessive recruitment of neutrophils extending the inflammatory phase of healing, and the gene expression of neutrophil attracting chemokines MIP-2 and KC. However, restraint stress did not affect macrophage infiltration. Stress decreased the phagocytic abilities of phagocytic cells ex vivo, yet it did not affect superoxide production. The cell surface expression of adhesion molecules CD11b and TLR4 were decreased in peripheral blood monocytes in stressed mice. The phenotype of macrophages present at the wound site was also altered. Gene expression of markers of pro-inflammatory classically activated macrophages, CXCL10 and CCL5, were down-regulated; as were markers associated with wound healing macrophages, CCL22, IGF-1, RELMα; and the regulatory macrophage marker, chemokine CCL1. Restraint stress also induced up-regulation of IL10 gene expression. In summary, our study has shown that restraint stress suppresses the phenotype shift of the macrophage population, as compared to the changes observed during normal wound healing, while the number of macrophages remains constant. We also observed a general suppression of chemokine gene expression. Modulation of the macrophage phenotype could provide a new therapeutic approach in the treatment of wounds under stress conditions in the clinical setting.

  11. Traumatic Stress Disorders and Risk of Subsequent Schizophrenia Spectrum Disorder or Bipolar Disorder: A Nationwide Cohort Study.

    PubMed

    Okkels, Niels; Trabjerg, Betina; Arendt, Mikkel; Pedersen, Carsten Bøcker

    2017-01-01

    Traumatic stress disorders are prevalent in patients with schizophrenia and bipolar disorder. However, there is a lack of prospective longitudinal studies investigating the risk of severe mental illness for people diagnosed with traumatic stress disorders. We aimed to assess if patients with acute stress reaction (ASR) or post-traumatic stress disorder (PTSD) are at increased risk of schizophrenia spectrum disorders or bipolar disorder. We performed a prospective cohort study covering the entire Danish population including information on inpatient and outpatient mental hospitals over 2 decades. Predictors were in- or outpatient diagnoses of ASR or PTSD. We calculated incidence rate ratios (IRR) with 95% CIs of schizophrenia, schizophrenia spectrum disorder, and bipolar disorder. Persons with a traumatic stress disorder had a significantly increased risk of schizophrenia (IRR 3.80, CI 2.33-5.80), schizophrenia spectrum disorder (IRR 2.34, CI 1.46-3.53), and bipolar disorder (IRR 4.22, CI 2.25-7.13). Risks were highest in the first year after diagnosis of the traumatic stress disorder and remained significantly elevated after more than 5 years. Mental illness in a parent could not explain the association. Our findings support an association between diagnosed traumatic stress disorders and subsequent schizophrenia spectrum disorder or bipolar disorder. If replicated, this may increase clinical focus on patients with traumatic stress disorders. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  12. Integrated circuits and molecular components for stress and feeding: implications for eating disorders

    PubMed Central

    Hardaway, J. A.; Crowley, N. A.; Bulik, C. M.; Kash, T. L.

    2015-01-01

    Eating disorders are complex brain disorders that afflict millions of individuals worldwide. The etiology of these diseases is not fully understood, but a growing body of literature suggests that stress and anxiety may play a critical role in their development. As our understanding of the genetic and environmental factors that contribute to disease in clinical populations like anorexia nervosa, bulimia nervosa and binge eating disorder continue to grow, neuroscientists are using animal models to understand the neurobiology of stress and feeding. We hypothesize that eating disorder clinical phenotypes may result from stress-induced maladaptive alterations in neural circuits that regulate feeding, and that these circuits can be neurochemically isolated using animal model of eating disorders. PMID:25366309

  13. Integrated circuits and molecular components for stress and feeding: implications for eating disorders.

    PubMed

    Hardaway, J A; Crowley, N A; Bulik, C M; Kash, T L

    2015-01-01

    Eating disorders are complex brain disorders that afflict millions of individuals worldwide. The etiology of these diseases is not fully understood, but a growing body of literature suggests that stress and anxiety may play a critical role in their development. As our understanding of the genetic and environmental factors that contribute to disease in clinical populations like anorexia nervosa, bulimia nervosa and binge eating disorder continue to grow, neuroscientists are using animal models to understand the neurobiology of stress and feeding. We hypothesize that eating disorder clinical phenotypes may result from stress-induced maladaptive alterations in neural circuits that regulate feeding, and that these circuits can be neurochemically isolated using animal model of eating disorders. © 2014 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  14. Substance abuse, memory, and post-traumatic stress disorder

    PubMed Central

    Tipps, Megan E.; Raybuck, Jonathan D.; Lattal, K. Matthew

    2014-01-01

    A large body of literature demonstrates the effects of abused substances on memory. These effects differ depending on the drug, the pattern of delivery (acute or chronic), and the drug state at the time of learning or assessment. Substance use disorders involving these drugs are often comorbid with anxiety disorders, such as post-traumatic stress disorder (PTSD). When the cognitive effects of these drugs are considered in the context of the treatment of these disorders, it becomes clear that these drugs may play a deleterious role in the development, maintenance, and treatment of PTSD. In this review, we examine the literature evaluating the cognitive effects of three commonly abused drugs: nicotine, cocaine, and alcohol. These three drugs operate through both common and distinct neurobiological mechanisms and alter learning and memory in multiple ways. We consider how the cognitive and affective effects of these drugs interact with the acquisition, consolidation, and extinction of learned fear, and we discuss the potential impediments that substance abuse creates for the treatment of PTSD. PMID:24345414

  15. Neuroimaging genetic approaches to Posttraumatic Stress Disorder.

    PubMed

    Lebois, Lauren A M; Wolff, Jonathan D; Ressler, Kerry J

    2016-10-01

    Neuroimaging genetic studies that associate genetic and epigenetic variation with neural activity or structure provide an opportunity to link genes to psychiatric disorders, often before psychopathology is discernable in behavior. Here we review neuroimaging genetics studies with participants who have Posttraumatic Stress Disorder (PTSD). Results show that genes related to the physiological stress response (e.g., glucocorticoid receptor and activity, neuroendocrine release), learning and memory (e.g., plasticity), mood, and pain perception are tied to neural intermediate phenotypes associated with PTSD. These genes are associated with and sometimes predict neural structure and function in areas involved in attention, executive function, memory, decision-making, emotion regulation, salience of potential threats, and pain perception. Evidence suggests these risk polymorphisms and neural intermediate phenotypes are vulnerabilities toward developing PTSD in the aftermath of trauma, or vulnerabilities toward particular symptoms once PTSD has developed. Work distinguishing between the re-experiencing and dissociative sub-types of PTSD, and examining other PTSD symptom clusters in addition to the re-experiencing and hyperarousal symptoms, will further clarify neurobiological mechanisms and inconsistent findings. Furthermore, an exciting possibility is that genetic associations with PTSD may eventually be understood through differential intermediate phenotypes of neural circuit structure and function, possibly underlying the different symptom clusters seen within PTSD. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Effects of prenatal restraint stress on the hypothalamus-pituitary-adrenal axis and related behavioural and neurobiological alterations.

    PubMed

    Maccari, Stefania; Morley-Fletcher, Sara

    2007-08-01

    Chronic hyper-activation of the hypothalamus-pituitary axis is associated with the suppression of reproductive, growth, thyroid and immune functions that may lead to various pathological states. Although many individuals experiencing stressful events do not develop pathologies, stress seems to be a provoking factor in those individuals with particular vulnerability, determined by genetic factors or earlier experience. Exposure of the developing brain to severe and/or prolonged stress may result in hyper-activity of the stress system, defective glucocorticoids-negative feedback, altered cognition, novelty seeking, increased vulnerability to addictive behaviour, and mood-related disorders. Therefore, stress-related events that occur in the perinatal period can permanently change brain and behaviour of the developing individual. Prenatal restraint stress (PRS) in rats is a well-documented model of early stress known to induce long-lasting neurobiological and behavioural alterations including impaired feedback mechanisms of the HPA axis, disruption of circadian rhythms and altered neuroplasticity. Chronic treatments with antidepressants at adulthood have proven high predictive validity of the PRS rat as animal model of depression and, reinforce the idea of the usefulness of the PRS rat as an interesting animal model for the design and testing of new pharmacologic strategies in the treatment of stress-related disorders.

  17. Altered localization of amyloid precursor protein under endoplasmic reticulum stress.

    PubMed

    Kudo, Takashi; Okumura, Masayo; Imaizumi, Kazunori; Araki, Wataru; Morihara, Takashi; Tanimukai, Hitoshi; Kamagata, Eiichiro; Tabuchi, Nobuhiko; Kimura, Ryo; Kanayama, Daisuke; Fukumori, Akio; Tagami, Shinji; Okochi, Masayasu; Kubo, Mikiko; Tanii, Hisashi; Tohyama, Masaya; Tabira, Takeshi; Takeda, Masatoshi

    2006-06-02

    Recent reports have shown that the endoplasmic reticulum (ER) stress is relevant to the pathogenesis of Alzheimer disease. Following the amyloid cascade hypothesis, we therefore attempted to investigate the effects of ER stress on amyloid-beta peptide (Abeta) generation. In this study, we found that ER stress altered the localization of amyloid precursor protein (APP) from late compartments to early compartments of the secretory pathway, and decreased the level of Abeta 40 and Abeta 42 release by beta- and gamma-cutting. Transient transfection with BiP/GRP78 also caused a shift of APP and a reduction in Abeta secretion. It was revealed that the ER stress response facilitated binding of BiP/GRP78 to APP, thereby causing it to be retained in the early compartments apart from a location suitable for the cleavages of Abeta. These findings suggest that induction of BiP/GRP78 during ER stress may be one of the regulatory mechanisms of Abeta generation.

  18. Peripheral Biomarker Candidates of Posttraumatic Stress Disorder

    PubMed Central

    Kang, Hee Jin; Lyoo, In Kyoon

    2015-01-01

    There is high variability in the manifestation of physical and mental health problems following exposure to trauma and disaster. Although most people may show a range of acute symptoms in the aftermath of traumatic events, chronic and persistent mental disorders may not be developed in all individuals who were exposed to traumatic events. The most common long-term pathological consequence after trauma exposure is posttraumatic stress disorder (PTSD). However, comorbid conditions including depression, anxiety disorder, substance use-related problems, and a variety of other symptoms may frequently be observed in individuals with trauma exposure. Post-traumatic syndrome (PTS) is defined collectively as vast psychosocial problems that could be experienced in response to traumatic events. It is important to predict who will continue to suffer from physical and mental health problems and who will recover following trauma exposure. However, given the heterogeneity and variability in symptom manifestations, it is difficult to find identify biomarkers which predict the development of PTSD. In this review, we will summarize the results of recent studies with regard to putative biomarkers of PTSD and suggest future research directions for biomarker discovery for PTSD. PMID:26412967

  19. Post-Traumatic Stress Disorder and the Canadian Vietnam Veteran

    DTIC Science & Technology

    1989-03-30

    Documentation Page, DD Form 1473 (is)(is not) attached. Title Post - Traumatic Stress Disorder and the Canadian Vietnam Veteran Author(s) Robert H. Stretch...EDITIONS WILL BE USED U. Post - Traumatic Stress Disorder and the Canadian Vietnam Veteran MAJ Robert H. Stretch, Ph.D. U.S. Army Medical R&D Command... Post - Traumatic Stress Disorder (PTSD). PTSD results from exposure to trauma that is generally outside the range of normal human experience. It is

  20. Microbiota alteration is associated with the development of stress-induced despair behavior.

    PubMed

    Marin, Ioana A; Goertz, Jennifer E; Ren, Tiantian; Rich, Stephen S; Onengut-Gumuscu, Suna; Farber, Emily; Wu, Martin; Overall, Christopher C; Kipnis, Jonathan; Gaultier, Alban

    2017-03-07

    Depressive disorders often run in families, which, in addition to the genetic component, may point to the microbiome as a causative agent. Here, we employed a combination of behavioral, molecular and computational techniques to test the role of the microbiota in mediating despair behavior. In chronically stressed mice displaying despair behavior, we found that the microbiota composition and the metabolic signature dramatically change. Specifically, we observed reduced Lactobacillus and increased circulating kynurenine levels as the most prominent changes in stressed mice. Restoring intestinal Lactobacillus levels was sufficient to improve the metabolic alterations and behavioral abnormalities. Mechanistically, we identified that Lactobacillus-derived reactive oxygen species may suppress host kynurenine metabolism, by inhibiting the expression of the metabolizing enzyme, IDO1, in the intestine. Moreover, maintaining elevated kynurenine levels during Lactobacillus supplementation diminished the treatment benefits. Collectively, our data provide a mechanistic scenario for how a microbiota player (Lactobacillus) may contribute to regulating metabolism and resilience during stress.

  1. Microbiota alteration is associated with the development of stress-induced despair behavior

    PubMed Central

    Marin, Ioana A.; Goertz, Jennifer E.; Ren, Tiantian; Rich, Stephen S.; Onengut-Gumuscu, Suna; Farber, Emily; Wu, Martin; Overall, Christopher C.; Kipnis, Jonathan; Gaultier, Alban

    2017-01-01

    Depressive disorders often run in families, which, in addition to the genetic component, may point to the microbiome as a causative agent. Here, we employed a combination of behavioral, molecular and computational techniques to test the role of the microbiota in mediating despair behavior. In chronically stressed mice displaying despair behavior, we found that the microbiota composition and the metabolic signature dramatically change. Specifically, we observed reduced Lactobacillus and increased circulating kynurenine levels as the most prominent changes in stressed mice. Restoring intestinal Lactobacillus levels was sufficient to improve the metabolic alterations and behavioral abnormalities. Mechanistically, we identified that Lactobacillus-derived reactive oxygen species may suppress host kynurenine metabolism, by inhibiting the expression of the metabolizing enzyme, IDO1, in the intestine. Moreover, maintaining elevated kynurenine levels during Lactobacillus supplementation diminished the treatment benefits. Collectively, our data provide a mechanistic scenario for how a microbiota player (Lactobacillus) may contribute to regulating metabolism and resilience during stress. PMID:28266612

  2. Addiction as a stress surfeit disorder.

    PubMed

    Koob, George F; Buck, Cara L; Cohen, Ami; Edwards, Scott; Park, Paula E; Schlosburg, Joel E; Schmeichel, Brooke; Vendruscolo, Leandro F; Wade, Carrie L; Whitfield, Timothy W; George, Olivier

    2014-01-01

    Drug addiction has been conceptualized as a chronically relapsing disorder of compulsive drug seeking and taking that progresses through three stages: binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation. Drug addiction impacts multiple motivational mechanisms and can be conceptualized as a disorder that progresses from positive reinforcement (binge/intoxication stage) to negative reinforcement (withdrawal/negative affect stage). The construct of negative reinforcement is defined as drug taking that alleviates a negative emotional state. Our hypothesis is that the negative emotional state that drives such negative reinforcement is derived from dysregulation of key neurochemical elements involved in the brain stress systems within the frontal cortex, ventral striatum, and extended amygdala. Specific neurochemical elements in these structures include not only recruitment of the classic stress axis mediated by corticotropin-releasing factor (CRF) in the extended amygdala as previously hypothesized but also recruitment of dynorphin-κ opioid aversive systems in the ventral striatum and extended amygdala. Additionally, we hypothesized that these brain stress systems may be engaged in the frontal cortex early in the addiction process. Excessive drug taking engages activation of CRF not only in the extended amygdala, accompanied by anxiety-like states, but also in the medial prefrontal cortex, accompanied by deficits in executive function that may facilitate the transition to compulsive-like responding. Excessive activation of the nucleus accumbens via the release of mesocorticolimbic dopamine or activation of opioid receptors has long been hypothesized to subsequently activate the dynorphin-κ opioid system, which in turn can decrease dopaminergic activity in the mesocorticolimbic dopamine system. Blockade of the κ opioid system can also block anxiety-like and reward deficits associated with withdrawal from drugs of abuse and block the

  3. Systems Biology Approach to Understanding Post-traumatic Stress Disorder

    DTIC Science & Technology

    2015-01-14

    post-traumatic stress disorder 5a. CONTRACT NUMBER W911NF-10-2-0111 & USAMRMC 09284002 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...Chemistry 2015 14. ABSTRACT Post-traumatic stress disorder (PTSD) is a psychological disorder a???ecting individuals that have experienced life-changing...functioning. Although PTSD is still categorized as a psychological disorder , recent years have witnessed a multi-directional research e???ort

  4. Altered brain activity during emotional empathy in somatoform disorder.

    PubMed

    de Greck, Moritz; Scheidt, Lisa; Bölter, Annette F; Frommer, Jörg; Ulrich, Cornelia; Stockum, Eva; Enzi, Björn; Tempelmann, Claus; Hoffmann, Thilo; Han, Shihui; Northoff, Georg

    2012-11-01

    Somatoform disorder patients suffer from impaired emotion recognition and other emotional deficits. Emotional empathy refers to the understanding and sharing of emotions of others in social contexts. It is likely that the emotional deficits of somatoform disorder patients are linked to disturbed empathic abilities; however, little is known so far about empathic deficits of somatoform patients and the underlying neural mechanisms. We used fMRI and an empathy paradigm to investigate 20 somatoform disorder patients and 20 healthy controls. The empathy paradigm contained facial pictures expressing anger, joy, disgust, and a neutral emotional state; a control condition contained unrecognizable stimuli. In addition, questionnaires testing for somatization, alexithymia, depression, empathy, and emotion recognition were applied. Behavioral results confirmed impaired emotion recognition in somatoform disorder and indicated a rather distinct pattern of empathic deficits of somatoform patients with specific difficulties in "empathic distress." In addition, somatoform patients revealed brain areas with diminished activity in the contrasts "all emotions"-"control," "anger"-"control," and "joy"-"control," whereas we did not find brain areas with altered activity in the contrasts "disgust"-"control" and "neutral"-"control." Significant clusters with less activity in somatoform patients included the bilateral parahippocampal gyrus, the left amygdala, the left postcentral gyrus, the left superior temporal gyrus, the left posterior insula, and the bilateral cerebellum. These findings indicate that disturbed emotional empathy of somatoform disorder patients is linked to impaired emotion recognition and abnormal activity of brain regions responsible for emotional evaluation, emotional memory, and emotion generation. Copyright © 2011 Wiley Periodicals, Inc.

  5. Striatal Functional Alteration During Incentive Anticipation in Pediatric Anxiety Disorders

    PubMed Central

    Guyer, Amanda E.; Choate, Victoria R.; Detloff, Allison; Benson, Brenda; Nelson, Eric E.; Perez-Edgar, Koraly; Fox, Nathan A.; Pine, Daniel S.; Ernst, Monique

    2012-01-01

    Objective Behavioral inhibition is an early childhood temperament recently associated with altered striatal response in adolescence to incentives of increasing magnitudes. Since early childhood behavioral inhibition is also associated with risk for adolescent social phobia, a similar pattern of striatal activation may manifest in social phobia. The present study compares striatal function in healthy adolescents, adolescents with social phobia, and adolescents with generalized anxiety disorder. Method Blood-oxygen-level-dependent signal in striatal regions was examined in 58 medication-free adolescents—14 with social phobia, 18 with generalized anxiety disorder but not social phobia, and 26 with no psychiatric disorder—matched on sex, age, puberty, IQ, and socioeconomic status. During functional magnetic resonance imaging, participants responded to incentive cues depicting potential monetary gains or losses of varying magnitudes. Results While anticipating incentives of increasing magnitude, adolescents with social phobia showed increasingly heightened caudate and putamen activation at a level greater than that seen in the healthy comparison and generalized anxiety disorder groups. The generalized anxiety disorder group showed a unique valence-specific putamen response relative to the healthy comparison or social phobia group. Both patient groups displayed more complex patterns in the nucleus accumbens than in the caudate or putamen. Conclusions Caudate and putamen hypersensitivity to incentives of increasing magnitudes characterizes adolescent social phobia, relative to activation in this region in adolescents with generalized anxiety disorder as well as healthy adolescents. Thus, these findings resemble the pattern previously found in adolescents with early childhood behavioral inhibition, thereby implicating similar neural responses to anticipation of incentives in both early childhood behavioral inhibition and adolescent social phobia. PMID:22423352

  6. Brain stimulation in posttraumatic stress disorder.

    PubMed

    Novakovic, Vladan; Sher, Leo; Lapidus, Kyle A B; Mindes, Janet; A Golier, Julia; Yehuda, Rachel

    2011-01-01

    Posttraumatic stress disorder (PTSD) is a complex, heterogeneous disorder that develops following trauma and often includes perceptual, cognitive, affective, physiological, and psychological features. PTSD is characterized by hyperarousal, intrusive thoughts, exaggerated startle response, flashbacks, nightmares, sleep disturbances, emotional numbness, and persistent avoidance of trauma-associated stimuli. The efficacy of available treatments for PTSD may result in part from relief of associated depressive and anxiety-related symptoms in addition to treatment of core symptoms that derive from reexperiencing, numbing, and hyperarousal. Diverse, heterogeneous mechanisms of action and the ability to act broadly or very locally may enable brain stimulation devices to address PTSD core symptoms in more targeted ways. To achieve this goal, specific theoretical bases derived from novel, well-designed research protocols will be necessary. Brain stimulation devices include both long-used and new electrical and magnetic devices. Electroconvulsive therapy (ECT) and Cranial electrotherapy stimulation (CES) have both been in use for decades; transcranial magnetic stimulation (TMS), magnetic seizure therapy (MST), deep brain stimulation (DBS), transcranial Direct Current Stimulation (tDCS), and vagus nerve stimulation (VNS) have been developed recently, over approximately the past twenty years. The efficacy of brain stimulation has been demonstrated as a treatment for psychiatric and neurological disorders such as anxiety (CES), depression (ECT, CES, rTMS, VNS, DBS), obsessive-compulsive disorder (OCD) (DBS), essential tremor, dystonia (DBS), epilepsy (DBS, VNS), Parkinson Disease (DBS), pain (CES), and insomnia (CES). To date, limited data on brain stimulation for PTSD offer only modest guidance. ECT has shown some efficacy in reducing comorbid depression in PTSD patients but has not been demonstrated to improve most core PTSD symptoms. CES and VNS have shown some efficacy in

  7. Stress and translocation: alterations in the stress physiology of translocated birds

    PubMed Central

    Dickens, Molly J.; Delehanty, David J.; Romero, L. Michael

    2009-01-01

    Translocation and reintroduction have become major conservation actions in attempts to create self-sustaining wild populations of threatened species. However, avian translocations have a high failure rate and causes for failure are poorly understood. While ‘stress’ is often cited as an important factor in translocation failure, empirical evidence of physiological stress is lacking. Here we show that experimental translocation leads to changes in the physiological stress response in chukar partridge, Alectoris chukar. We found that capture alone significantly decreased the acute glucocorticoid (corticosterone, CORT) response, but adding exposure to captivity and transport further altered the stress response axis (the hypothalamic–pituitary–adrenal axis) as evident from a decreased sensitivity of the negative feedback system. Animals that were exposed to the entire translocation procedure, in addition to the reduced acute stress response and disrupted negative feedback, had significantly lower baseline CORT concentrations and significantly reduced body weight. These data indicate that translocation alters stress physiology and that chronic stress is potentially a major factor in translocation failure. Under current practices, the restoration of threatened species through translocation may unwittingly depend on the success of chronically stressed individuals. This conclusion emphasizes the need for understanding and alleviating translocation-induced chronic stress in order to use most effectively this important conservation tool. PMID:19324794

  8. Social stress reactivity alters reward and punishment learning.

    PubMed

    Cavanagh, James F; Frank, Michael J; Allen, John J B

    2011-06-01

    To examine how stress affects cognitive functioning, individual differences in trait vulnerability (punishment sensitivity) and state reactivity (negative affect) to social evaluative threat were examined during concurrent reinforcement learning. Lower trait-level punishment sensitivity predicted better reward learning and poorer punishment learning; the opposite pattern was found in more punishment sensitive individuals. Increasing state-level negative affect was directly related to punishment learning accuracy in highly punishment sensitive individuals, but these measures were inversely related in less sensitive individuals. Combined electrophysiological measurement, performance accuracy and computational estimations of learning parameters suggest that trait and state vulnerability to stress alter cortico-striatal functioning during reinforcement learning, possibly mediated via medio-frontal cortical systems.

  9. Oxidative stress alters global histone modification and DNA methylation.

    PubMed

    Niu, Yingmei; DesMarais, Thomas L; Tong, Zhaohui; Yao, Yixin; Costa, Max

    2015-05-01

    The JmjC domain-containing histone demethylases can remove histone lysine methylation and thereby regulate gene expression. The JmjC domain uses iron Fe(II) and α-ketoglutarate (αKG) as cofactors in an oxidative demethylation reaction via hydroxymethyl lysine. We hypothesize that reactive oxygen species will oxidize Fe(II) to Fe(III), thereby attenuating the activity of JmjC domain-containing histone demethylases. To minimize secondary responses from cells, extremely short periods of oxidative stress (3h) were used to investigate this question. Cells that were exposed to hydrogen peroxide (H2O2) for 3h exhibited increases in several histone methylation marks including H3K4me3 and decreases of histone acetylation marks including H3K9ac and H4K8ac; preincubation with ascorbate attenuated these changes. The oxidative stress level was measured by generation of 2',7'-dichlorofluorescein, GSH/GSSG ratio, and protein carbonyl content. A cell-free system indicated that H2O2 inhibited histone demethylase activity where increased Fe(II) rescued this inhibition. TET protein showed a decreased activity under oxidative stress. Cells exposed to a low-dose and long-term (3 weeks) oxidative stress also showed increased global levels of H3K4me3 and H3K27me3. However, these global methylation changes did not persist after washout. The cells exposed to short-term oxidative stress also appeared to have higher activity of class I/II histone deacetylase (HDAC) but not class III HDAC. In conclusion, we have found that oxidative stress transiently alters the epigenetic program process through modulating the activity of enzymes responsible for demethylation and deacetylation of histones.

  10. Recent Advances in the Study of Sleep in the Anxiety Disorders, Obsessive-Compulsive Disorder, and Posttraumatic Stress Disorder.

    PubMed

    Boland, Elaine M; Ross, Richard J

    2015-12-01

    Sleep disturbance is frequently associated with generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, and posttraumatic stress disorder. This article reviews recent advances in understanding the mechanisms of the sleep disturbances in these disorders and discusses the implications for developing improved treatments. Published by Elsevier Inc.

  11. Oxidative stress alters physiological and morphological neuronal properties.

    PubMed

    Hasan, Sonia M; Joe, Mary; Alshuaib, Waleed B

    2007-07-01

    We investigated the effects of H(2)O(2)-induced oxidative stress on the delayed-rectifier current (IK(DR)), neuronal physiological and morphological properties. Measurements were obtained from hippocampal CA1 neurons in control solution and from the same neurons after exposure to oxidative stress (short- and long-term H(2)O(2) external applications at 0.1, 1, and 10 mM). With short-term (6 min) H(2)O(2) (1 mM) treatment, IK(DR) measured in the H(2)O(2)-containing solution (778 +/- 23 pA, n=20), was smaller than that measured in the control Ca(2+)-free Hepes solution (1,112 +/- 38 pA, n=20). Coenzyme Q(10) (0.1 mM) pretreatment prevented the H(2)O(2)-induced inhibition of IK(DR). With long-term (40, 80 min) H(2)O(2) (0.1, 10 mM) treatment, the neuron lost its distinctive shape (rounded up) and the neurite almost disappeared. These results suggest that oxidative stress, which inhibits IK(DR), can alter neural activity. The morphological changes caused by H(2)O(2) support the idea that oxidative stress causes intracellular damage and compromises neural function.

  12. Posttraumatic stress disorder and posttraumatic stress disorder-like symptoms and mild traumatic brain injury.

    PubMed

    Kennedy, Jan E; Jaffee, Michael S; Leskin, Gregory A; Stokes, James W; Leal, Felix O; Fitzpatrick, Pamela J

    2007-01-01

    In this article, we review the literature on posttraumatic stress disorder (PTSD) and PTSD-like symptoms that can occur along with mild traumatic brain injury (TBI) and concussion, with specific reference to concussive injuries in the military. We address four major areas: (1) clinical aspects of TBI and PTSD, including diagnostic criteria, incidence, predictive factors, and course; (2) biological overlap between PTSD and TBI; (3) comorbidity between PTSD and other mental disorders that can occur after mild TBI; and (4) current treatments for PTSD, with specific considerations related to treatment for patients with mild TBI or concussive injuries.

  13. Acute and post-traumatic stress disorder after spontaneous abortion.

    PubMed

    Bowles, S V; James, L C; Solursh, D S; Yancey, M K; Epperly, T D; Folen, R A; Masone, M

    2000-03-15

    When a spontaneous abortion is followed by complicated bereavement, the primary care physician may not consider the diagnosis of acute stress disorder or post-traumatic stress disorder. The major difference between these two conditions is that, in acute stress disorder, symptoms such as dissociation, reliving the trauma, avoiding stimuli associated with the trauma and increased arousal are present for at least two days but not longer than four weeks. When the symptoms persist beyond four weeks, the patient may have post-traumatic stress disorder. The symptoms of distress response after spontaneous abortion include psychologic, physical, cognitive and behavioral effects; however, patients with distress response after spontaneous abortion often do not meet the criteria for acute or post-traumatic stress disorder. After spontaneous abortion, as many as 10 percent of women may have acute stress disorder and up to 1 percent may have post-traumatic stress disorder. Critical incident stress debriefing, which may be administered by trained family physicians or mental health practitioners, may help patients who are having a stress disorder after a spontaneous abortion.

  14. Pain flashbacks in posttraumatic stress disorder.

    PubMed

    Salomons, Timothy V; Osterman, Janet E; Gagliese, Lucia; Katz, Joel

    2004-01-01

    Surgical patients who regain consciousness while under general anesthesia may develop symptoms of Posttraumatic Stress Disorder (PTSD). One common PTSD symptom is the experiencing of abnormal perceptions during which the patient feels as if the trauma is recurring. The objective of this report is to document the re-occurrence of pain as part of the PTSD sequelae. We present two patients who developed PTSD following an episode of awareness under anesthesia. In both cases, posttraumatic sequelae persisted for years and included pain symptoms that resembled, in quality and location, pain experienced during surgery. In addition to their similarity to the original pain, these pain symptoms were triggered by stimuli associated with the traumatic situation, suggesting that they were flashbacks to the episode of awareness under anesthesia. The similarity between the patients' pain symptoms and pain experienced during trauma, the triggering by traumatic cues, and the associated emotional arousal and avoidance suggest the involvement of a somatosensory memory mechanism.

  15. Tribulin in post-traumatic stress disorder.

    PubMed

    Davidson, J; Glover, V; Clow, A; Kudler, H; Meador, K; Sandler, M

    1988-11-01

    Tribulin (endogenous monoamine oxidase inhibitor/benzodiazepine receptor binding inhibitor) output was measured in the urine of 18 patients with post-traumatic stress disorder (PTSD) and 13 controls. The level of the two inhibitory activities was highly significantly correlated in the group as a whole. There was no difference between output of either inhibitor in patients and controls. However, when the PTSD group was subdivided according to various psychometric ratings, a pattern of output did emerge. Levels of both inhibitory activities were higher in agitated compared with non-agitated subjects, and lower in extroverts compared with introverts. This finding supports the view that tribulin output is raised in conditions of greater arousal.

  16. Social Bonds and Posttraumatic Stress Disorder

    PubMed Central

    Charuvastra, Anthony; Cloitre, Marylene

    2009-01-01

    Retrospective and prospective studies consistently show that individuals exposed to human-generated traumatic events carry a higher risk of developing Posttraumatic Stress Disorder (PTSD) than those exposed to other kinds of events. These studies also consistently identify perceptions of social support both before and after a traumatic event as an important factor in the determining vulnerability to the development of PTSD. We review the literature on interpersonal traumas, social support and risk for PTSD and integrate findings with recent advances in developmental psychopathology, attachment theory and social neuroscience. We propose and gather evidence for what we term the social ecology of PTSD, a conceptual framework for understanding how both PTSD risk and recovery are highly dependent on social phenomena. We explore clinical implications of this conceptual framework. PMID:17883334

  17. Posttraumatic Stress Disorder: Emerging Concepts of Pharmacotherapy

    PubMed Central

    Baker, Dewleen G.; Nievergelt, Caroline M.; Risbrough, Victoria B.

    2009-01-01

    Posttraumatic stress disorder (PTSD) can result from a traumatic experience that elicits emotions of fear, helpless or horror. Most individuals remain asymptomatic or symptoms quickly resolve, but in a minority intrusive imagery and nightmares, emotional numbing and avoidance, and hyperarousal persist for decades. PTSD is associated with psychiatric and medical co-morbidities, increased risk for suicide, and with poor social and occupational functioning. Psychotherapy and pharmacotherapy are common treatments. Whereas, research supports the efficacy of the cognitive behavioral psychotherapies, there is insufficient evidence to unequivocally support the efficacy of any specific pharmacotherapy. Proven effective pharmacologic agents are sorely needed to treat core and targeted PTSD symptoms, and for prevention. This review describes current and emerging pharmacotherapies that advance these goals. PMID:19453285

  18. Posttraumatic Stress Disorder and Orofacial Pain

    PubMed Central

    Prica, Natalija; Shejbal, Dražen

    2015-01-01

    Chronic orofacial pain occurs frequently in patients with posttraumatic stress disorder (PTSD) and at the same time any pathological process involving orofacial area can be reflected in emotional interpretation of pain and can trigger a series of reactions associated with the PTSD group of symptoms in patients with PTSD. Painful stimuli caused in this way may occur after the primary cause ceased, and because of convergence can cause referred pain outside of the anatomical site where the primary injury occurred. Chronic orofacial pain and PTSD are diagnosed on the basis of subjective testimony and this regularly occurs in the context of social interaction between patients, doctors, medical staff or researchers making it difficult to standardize the results and introduces many cultural phenomena. PMID:27688386

  19. Postdoctoral training in posttraumatic stress disorder research.

    PubMed

    Sloan, Denise M; Vogt, Dawne; Wisco, Blair E; Keane, Terence M

    2015-03-01

    Postdoctoral training is increasingly common in the field of psychology. Although many individuals pursue postdoctoral training in psychology, guidelines for research training programs at this level do not exist. The rapid advances in the field, particularly with respect to genetics, neuroimaging, and data analytic approaches, require clinical scientists to possess knowledge and expertise across a broad array of areas. Postdoctoral training is often needed to acquire such a skill set. This paper describes a postdoctoral training program designed for individuals pursuing academic careers in traumatic stress disorders research. In this paper, we describe the structure of our training program, challenges we have faced during the 15 years of its existence, and how we have addressed these challenges. We conclude with a presentation of outcome data for the training program and a discussion of how training programs in other settings might be structured. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

  20. Structural and functional alterations to rat medial prefrontal cortex following chronic restraint stress and recovery

    PubMed Central

    Goldwater, Deena S.; Pavlides, Constantine; Hunter, Richard G.; Bloss, Erik B.; Hof, Patrick R.; McEwen, Bruce S.; Morrison, John H.

    2009-01-01

    Chronic stress has been shown in animal models to result in altered dendritic morphology of pyramidal neurons of the medial prefrontal cortex (mPFC). It has been hypothesized that the stress-induced dendritic retractions and spine loss lead to disrupted connectivity that results in stress-induced functional impairment of mPFC. While these alterations were initially viewed as a neurodegenerative event, it has recently been established that stress induced dendritic alterations are reversible if animals are given time to recover from chronic stress. However, whether spine growth accompanies dendritic extension remains to be demonstrated. It is also not known if recovery-phase dendritic extension allows for re-establishment of functional capacity. The goal of this study, therefore, was to characterize the structural and functional effects of chronic stress and recovery on the infralimbic (IL) region of the rat mPFC. We compared neuronal morphology of layer V IL pyramidal neurons from animals subjected to 21 days of chronic restraint stress (CRS) to those that experienced CRS followed by a 21 day recovery period. Layer V pyramidal cell functional capacity was assessed by intra-IL long-term potentiation (LTP) both in the absence and presence of SKF38393, a dopamine receptor partial agonist and a known PFC LTP modulator. We found that stress-induced IL apical dendritic retraction and spine loss co-occur with receptor-mediated impairments to catecholaminergic facilitation of synaptic plasticity. We also found that while post-stress recovery did not reverse distal dendritic retraction, it did result in over-extension of proximal dendritic neuroarchitecture and spine growth as well as a full reversal of CRS-induced impairments to catecholaminergic-mediated synaptic plasticity. Our results support the hypothesis that disease-related PFC dysfunction is a consequence of network disruption secondary to altered structural and functional plasticity and that circuitry

  1. Cardiovascular manifestations of posttraumatic stress disorder.

    PubMed Central

    Bedi, Updesh Singh; Arora, Rohit

    2007-01-01

    Posttraumatic stress disorder (PTSD) involves the onset of psychiatric symptoms after exposure to a traumatic event. PTSD has an estimated lifetime prevalence of 7.8% among adult Americans, and about 15.2% of the men and 8.5% of the women who served in Vietnam suffered from posttraumatic stress disorder (PTSD) > or =15 years after their military service. Physiological responses (increase in heart rate, blood pressure, tremor and other symptoms of autonomic arousal) to reminders of the trauma are a part of the DSM-IV definition of PTSD. Multiple studies have shown that patients suffering from PTSD have increased resting heart rate, increased startle reaction, and increased heart rate and blood pressure as responses to traumatic slides, sounds and scripts. Some researchers have studied the sympathetic nervous system even further by looking at plasma norepinephrine and 24-hour urinary norepinephrine and found them to be elevated in veterans with PTSD as compared to those without PTSD. PTSD is associated with hyperfunctioning of the central noradrenergic system. Hyperactivity of the sympathoadrenal axis might contribute to cardiovascular disease through the effects of the catecholamines on the heart, the vasculature and platelet function. A psychobiological model based on allostatic load has also been proposed and states that chronic stressors over long durations of time lead to increased neuroendocrine responses, which have adverse effects on the body. PTSD has also been shown to be associated with an increased prevalence of substance abuse. With this review, we have discussed the effects of PTSD on the cardiovascular system. PMID:17595933

  2. Sex Differences in Stress-Related Psychiatric Disorders: Neurobiological Perspectives

    PubMed Central

    Bangasser, Debra A.; Valentino, Rita J.

    2014-01-01

    Stress is associated with the onset and severity of several psychiatric disorders that occur more frequently in women than men, including posttraumatic stress disorder (PTSD) and depression. Patients with these disorders present with dysregulation of several stress response systems, including the neuroendocrine response to stress, corticolimbic responses to negatively valenced stimuli, and hyperarousal. Thus, sex differences within their underlying circuitry may explain sex biases in disease prevalence. This review describes clinical studies that identify sex differences within the activity of these circuits, as well as preclinical studies that demonstrate cellular and molecular sex differences in stress responses systems. These studies reveal sex differences from the molecular to the systems level that increase endocrine, emotional, and arousal responses to stress in females. Exploring these sex differences is critical because this research can reveal the neurobiological underpinnings of vulnerability to stress-related psychiatric disorders and guide the development of novel pharmacotherapies. PMID:24726661

  3. Post-traumatic stress disorder and opioid use disorder: A narrative review of conceptual models.

    PubMed

    Danovitch, Itai

    2016-01-01

    Post-traumatic stress disorder is highly prevalent among individuals who suffer from opioid use disorder. Compared to individuals with opioid use disorder alone, those with post-traumatic stress disorder have a worse course of illness, occupational functioning, and physical health. The neurobiological pathways underlying each disorder overlap substantially, and there are multiple pathways through which these disorders may interact. This narrative review explores evidence underpinning 3 explanatory perspectives on comorbid post-traumatic stress disorder and opioid use disorder: The opioid susceptibility model (a.k.a.: the Self-Medication Hypothesis), the post-traumatic stress disorder susceptibility model, and the common factors model. Diagnostic implications, treatment implications, and directions for future research are discussed.

  4. Posttraumatic stress disorder among Hispanic Vietnam veterans.

    PubMed

    Ortega, A N; Rosenheck, R

    2000-04-01

    The purpose of this study was to examine posttraumatic stress disorder (PTSD) among Hispanics who served in the Vietnam War. The authors conducted secondary data analyses of the National Vietnam Veterans Readjustment Study, a national epidemiologic study completed in 1988 of a representative sample of veterans who served during the Vietnam era (N=1,195). After adjustment for premilitary and military experiences, the authors found that Hispanic, particularly Puerto Rican, Vietnam veterans had significantly more severe PTSD symptoms and a higher probability of experiencing PTSD than nonminority veterans. However, they had no greater risk for other mental disorders, and their greater risk for PTSD was not explained by acculturation. Despite their more severe symptoms, Hispanic veterans, especially Puerto Rican veterans, showed no greater functional impairment than non-Hispanic white veterans. Hispanic Vietnam veterans, especially Puerto Rican Vietnam veterans, have a higher risk for PTSD and experience more severe PTSD symptoms than non-Hispanic white Vietnam veterans, and these differences are not explained by exposure to stressors or acculturation. This high level of symptoms was not accompanied by substantial reduction in functioning, suggesting that the observed differences in symptom reporting may reflect features of expressive style rather than different levels of illness.

  5. [Therapists' psychological problems when treating posttraumatic stress disorder].

    PubMed

    Kezić, Slobodanka; Mihanović, Mate; Molnar, Sven; Sain, Ivica

    2006-09-01

    War experience in interaction with personality structure can have a traumatic effect and provoke various psychopathological responses and even disorders at the psychological level. PTSD is one of the possible psychopathological responses to war trauma, which provokes a range of different emotions in those working with such patients. The heterogeneity of the clinical aspect of the disorder, the comorbidity and social malfunctioning of the patients represent a frequent source of difficulties in the psychiatrist's work. The disorder brings about alterations at the somatic, psychological, social and occupational level of the affected individual, requiring a complex approach to treatment. The psychotherapeutic treatment of PTSD patients gives rise to different counter-transfer emotions at different stages of the therapeutic process. The therapist experiences fright, anger, guilt, frustration, and sometimes even a tendency to avoid the patient. His ability for empathy and understanding of the patient can be exhausted and become the cause of a reduced capacity for sympathy, a secondary traumatic stress and a vicarious trauma.

  6. Buprenorphine Alters Inflammatory and Oxidative Stress Molecular Markers in Arthritis

    PubMed Central

    Hitchon, Carol

    2017-01-01

    Buprenorphine is recommended for use as an analgesic in animal models including in murine models of collagen-induced arthritis (CIA). However, the effect of buprenorphine on the expression of disease-associated biomarkers is not well defined. We examined the effect of buprenorphine administration on disease progression and the expression of inflammatory and oxidative stress markers, in a murine model of CIA. Buprenorphine administration altered the expression of cytokines, IFN-γ, IL-6, and MMP-3, and oxidative markers, for example, iNOS, superoxide dismutase (SOD1), and catalase (CAT), in the CIA mice. As buprenorphine is an analgesic, we further monitored the association of expression of these biomarkers with pain scores in a human cohort of early rheumatoid arthritis (RA). Serum MMP-3 levels and blood mRNA expression of antioxidants sod1 and cat correlated with pain scores in the RA cohort. We have demonstrated that administration of buprenorphine alters the expression of inflammatory and oxidative stress-related molecular markers in a murine model of CIA. This caveat needs to be considered in animal experiments using buprenorphine as an analgesic, as it can be a confounding factor in murine studies used for prediction of response to therapy. Furthermore, the antioxidant enzymes that showed an association with pain scores in the human cohort may be explored as biomarkers for pain in future studies. PMID:28572711

  7. Stress-Induced Permeability Alterations in an Argillaceous Limestone

    NASA Astrophysics Data System (ADS)

    Selvadurai, A. P. S.; Głowacki, A.

    2017-05-01

    The paper presents the results of experiments that were conducted to determine the influence of a triaxial stress state on the evolution of the permeability of an argillaceous limestone. The limestone rock is found in the Ordovician rock formations above the Precambrian basement located in southern Ontario, Canada, which is being considered as a potential host rock for the construction of a deep ground repository for storing low- and intermediate-level nuclear waste. The paper presents the results of an extensive series of hydraulic pulse tests and steady-state tests that were conducted to determine the permeability alterations in zones that can experience levels of damage that can be present in vicinity of an excavated underground opening. A "state-space" relationship is developed to describe permeability evolution with the triaxial stress in the pre-failure regime. The permeability evolution in extensively damaged post-failure states of the rock is also investigated. It is shown that permeability alterations were four orders of magnitude higher as a result of significant damage to the material, which is an important consideration in establishing the efficiency of the host rock formation as a barrier for the long-term containment of radionuclide migration.

  8. Stress-related disorders in African-American children.

    PubMed Central

    Bell, C. C.

    1997-01-01

    Children exposed to traumatic stress are vulnerable to a variety of stress-related disorders other than classical post-traumatic stress disorder. Several case histories are presented to illustrate some of the diversity of how traumatic stress may manifest in children. African-American children are the main focus of this article as political, economic, social, and morbidity and mortality indicators suggest that African-American children are at high risk for exposure to potentially traumatic stressors. Different presentations of traumatic, stress are discussed in an effort to broaden our understanding of the outcome of traumatic stress to fully help traumatized children. PMID:9170834

  9. [The post-traumatic stress disorder].

    PubMed

    Olff, Miranda

    2013-01-01

    Many people experience a potentially traumatic event during their lives, which can result in brief periods of post-traumatic stress symptoms; this is a normal reaction. Most people can deal with a traumatic event when supported by significant others, but 10% of them develop post-traumatic stress disorder (PTSD). The nature of the traumatic event, the duration of exposure and the age at which one experiences such an event partly determine whether a person will develop PTSD. Psychological debriefing (a single-session consultation) does not prevent the development of PTSD; it is therefore not useful to offer this to everyone who has experienced a traumatic event. New and promising developments have, however, arisen in this regard. Trauma-focused psychotherapy has proved to be effective for patients with PTSD, possibly in combination with medication. Individuals who experience many or severe initial symptoms after a traumatic event may benefit from early, short-term, trauma-focused psychotherapy for preventing the development of chronic PTSD. Developments pertaining to the DSM-5 pay more attention to 'complex' PTSD, a type which is often the result of long-term traumatisation during childhood.

  10. Low dose effects of a Withania somnifera extract on altered marble burying behavior in stressed mice

    PubMed Central

    Dey, Amitabha; Chatterjee, Shyam Sunder; Kumar, Vikas

    2016-01-01

    Aim: Withania somnifera root (WSR) extracts are often used in traditionally known Indian systems of medicine for prevention and cure of psychosomatic disorders. The reported experiment was designed to test whether low daily oral doses of such extracts are also effective in suppressing marble burying behavior in stressed mice or not. Materials and Methods: Groups of mice treated with 10, 20, or 40 mg/kg daily oral doses of WSR were subjected to a foot shock stress-induced hyperthermia test on the 1st, 5th, 7th, and 10th day of the experiment. On the 11th and 12th treatment days, they were subjected to marble burying tests. Stress response suppressing effects of low dose WSR were estimated by its effects on body weight and basal core temperature of animals during the course of the experiment. Results: Alterations in bodyweight and basal core temperature triggered by repeated exposures to foot shock stress were absent even in the 10 mg/kg/day WSR treated group, whereas the effectiveness of the extract in foot shock stress-induced hyperthermia and marble burying tests increased with its increasing daily dose. Conclusion: Marble burying test in stressed mice is well suited for identifying bioactive constituents of W. somnifera like medicinal plants with adaptogenic, anxiolytic and antidepressant activities, or for quantifying pharmacological interactions between them. PMID:27366354

  11. Stress-induced alterations in estradiol sensitivity increase risk for obesity in women.

    PubMed

    Michopoulos, Vasiliki

    2016-11-01

    The prevalence of obesity in the United States continues to rise, increasing individual vulnerability to an array of adverse health outcomes. One factor that has been implicated causally in the increased accumulation of fat and excess food intake is the activity of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis in the face of relentless stressor exposure. However, translational and clinical research continues to understudy the effects sex and gonadal hormones and LHPA axis dysfunction in the etiology of obesity even though women continue to be at greater risk than men for stress-induced disorders, including depression, emotional feeding and obesity. The current review will emphasize the need for sex-specific evaluation of the relationship between stress exposure and LHPA axis activity on individual risk for obesity by summarizing data generated by animal models currently being leveraged to determine the etiology of stress-induced alterations in feeding behavior and metabolism. There exists a clear lack of translational models that have been used to study female-specific risk. One translational model of psychosocial stress exposure that has proven fruitful in elucidating potential mechanisms by which females are at increased risk for stress-induced adverse health outcomes is that of social subordination in socially housed female macaque monkeys. Data from subordinate female monkeys suggest that increased risk for emotional eating and the development of obesity in females may be due to LHPA axis-induced changes in the behavioral and physiological sensitivity of estradiol. The lack in understanding of the mechanisms underlying these alterations necessitate the need to account for the effects of sex and gonadal hormones in the rationale, design, implementation, analysis and interpretation of results in our studies of stress axis function in obesity. Doing so may lead to the identification of novel therapeutic targets with which to combat stress-induced obesity

  12. Dissociative symptomatology in posttraumatic stress disorder and disorders of extreme stress.

    PubMed

    Zucker, Marla; Spinazzola, Joseph; Blaustein, Margaret; van der Kolk, Bessel A

    2006-01-01

    The present study was designed to assess differences in dissociative symptoms in adults with Posttraumatic Stress Disorder (PTSD) vs. PTSD plus Disorders of Extreme Stress Not Otherwise Specified (DESNOS). This study was done for two reasons: (1) to better understand the clinical profile of DESNOS clients in order to inform more effective treatment, and (2) to further empirical research on the validity of the DESNOS construct. To assess severity of dissociative symptoms, the authors administered the Dissociative Experiences Scale (DES) to 155 participants with PTSD. Using the Structured Interview for Disorders of Extreme Stress (SIDES), participants were divided into two groups: those who also met criteria for DESNOS and those who did not. DES means are provided for the two groups. Participants with PTSD plus DESNOS scored higher than participants with only PTSD on the measure of dissociative symptomatology, particularly on the DES scales that tap absorption/fantasy and depersonalization/derealization. The two groups did not differ on the amnesia subscale of the DES. Findings support the construct validity of the DESNOS concept and further delineate the clinical profiles of community-based PTSD with and without DESNOS, thus contributing to the knowledge base on the assessment of complex adaptations to trauma.

  13. Altered choroid plexus gene expression in major depressive disorder

    PubMed Central

    Turner, Cortney A.; Thompson, Robert C.; Bunney, William E.; Schatzberg, Alan F.; Barchas, Jack D.; Myers, Richard M.; Akil, Huda; Watson, Stanley J.

    2014-01-01

    Given the emergent interest in biomarkers for mood disorders, we assessed gene expression in the choroid plexus (CP), the region that produces cerebrospinal fluid (CSF), in individuals with major depressive disorder (MDD). Genes that are expressed in the CP can be secreted into the CSF and may be potential biomarker candidates. Given that we have previously shown that fibroblast growth factor family members are differentially expressed in post-mortem brain of subjects with MDD and the CP is a known source of growth factors in the brain, we posed the question whether growth factor dysregulation would be found in the CP of subjects with MDD. We performed laser capture microscopy of the CP at the level of the hippocampus in subjects with MDD and psychiatrically normal controls. We then extracted, amplified, labeled, and hybridized the cRNA to Illumina BeadChips to assess gene expression. In controls, the most highly abundant known transcript was transthyretin. Moreover, half of the 14 most highly expressed transcripts in controls encode ribosomal proteins. Using BeadStudio software, we identified 169 transcripts differentially expressed (p < 0.05) between control and MDD samples. Using pathway analysis we noted that the top network altered in subjects with MDD included multiple members of the transforming growth factor-beta (TGFβ) pathway. Quantitative real-time PCR (qRT-PCR) confirmed downregulation of several transcripts that interact with the extracellular matrix in subjects with MDD. These results suggest that there may be an altered cytoskeleton in the CP in MDD subjects that may lead to a disrupted blood-CSF-brain barrier. PMID:24795602

  14. Functional network topology associated with posttraumatic stress disorder in veterans.

    PubMed

    Kennis, M; van Rooij, S J H; van den Heuvel, M P; Kahn, R S; Geuze, E

    2016-01-01

    Posttraumatic stress disorder (PTSD) is a disabling disorder associated with resting state functional connectivity alterations. However, whether specific brain regions are altered in PTSD or whether the whole brain network organization differs remains unclear. PTSD can be treated with trauma-focused therapy, although only half of the patients recover after treatment. In order to better understand PTSD psychopathology our aim was to study resting state networks in PTSD before and after treatment. Resting state functional magnetic resonance images were obtained from veterans with PTSD (n = 50) and controls (combat and civilian controls; n = 54) to explore which network topology properties (degree and clustering coefficient) of which brain regions are associated with PTSD. Then, PTSD-associated brain regions were investigated before and after treatment. PTSD patients were subdivided in persistent (n = 22) and remitted PTSD patients (n = 17), and compared with combat controls (n = 22), who were also reassessed. Prior to treatment associations with PTSD were found for the degree of orbitofrontal, and temporoparietal brain regions, and for the clustering coefficient of the anterior cingulate cortex. No significant effects were found over the course of treatment. Our results are in line with previous resting state studies, showing resting state connectivity alterations in the salience network and default mode network in PTSD, and also highlight the importance of other brain regions. However, network metrics do not seem to change over the course of treatment. This study contributes to a better understanding of the psychopathology of PTSD.

  15. Functional network topology associated with posttraumatic stress disorder in veterans

    PubMed Central

    Kennis, M.; van Rooij, S.J.H.; van den Heuvel, M.P.; Kahn, R.S.; Geuze, E.

    2015-01-01

    Posttraumatic stress disorder (PTSD) is a disabling disorder associated with resting state functional connectivity alterations. However, whether specific brain regions are altered in PTSD or whether the whole brain network organization differs remains unclear. PTSD can be treated with trauma-focused therapy, although only half of the patients recover after treatment. In order to better understand PTSD psychopathology our aim was to study resting state networks in PTSD before and after treatment. Resting state functional magnetic resonance images were obtained from veterans with PTSD (n = 50) and controls (combat and civilian controls; n = 54) to explore which network topology properties (degree and clustering coefficient) of which brain regions are associated with PTSD. Then, PTSD-associated brain regions were investigated before and after treatment. PTSD patients were subdivided in persistent (n = 22) and remitted PTSD patients (n = 17), and compared with combat controls (n = 22), who were also reassessed. Prior to treatment associations with PTSD were found for the degree of orbitofrontal, and temporoparietal brain regions, and for the clustering coefficient of the anterior cingulate cortex. No significant effects were found over the course of treatment. Our results are in line with previous resting state studies, showing resting state connectivity alterations in the salience network and default mode network in PTSD, and also highlight the importance of other brain regions. However, network metrics do not seem to change over the course of treatment. This study contributes to a better understanding of the psychopathology of PTSD. PMID:26900570

  16. Alterations in the ribosomal machinery in cancer and hematologic disorders

    PubMed Central

    2012-01-01

    Ribosomes are essential components of the protein translation machinery and are composed of more than 80 unique large and small ribosomal proteins. Recent studies show that in addition to their roles in protein translation, ribosomal proteins are also involved in extra-ribosomal functions of DNA repair, apoptosis and cellular homeostasis. Consequently, alterations in the synthesis or functioning of ribosomal proteins can lead to various hematologic disorders. These include congenital anemias such as Diamond Blackfan anemia and Shwachman Diamond syndrome; both of which are associated with mutations in various ribosomal genes. Acquired uniallelic deletion of RPS14 gene has also been shown to lead to the 5q syndrome, a distinct subset of MDS associated with macrocytic anemia. Recent evidence shows that specific ribosomal proteins are overexpressed in liver, colon, prostate and other tumors. Ribosomal protein overexpression can promote tumorigenesis by interactions with the p53 tumor suppressor pathway and also by direct effects on various oncogenes. These data point to a broad role of ribosome protein alterations in hematologic and oncologic diseases. PMID:22709827

  17. Altered functional connectivity of interoception in illness anxiety disorder.

    PubMed

    Grossi, Dario; Longarzo, Mariachiara; Quarantelli, Mario; Salvatore, Elena; Cavaliere, Carlo; De Luca, Paolofabrizio; Trojano, Luigi; Aiello, Marco

    2017-01-01

    Interoception collects all information coming from the body and is sustained by several brain areas such as insula and cingulate cortex. Here, we used resting-state functional magnetic resonance imaging to investigate functional connectivity (FC) of networks implied in interoception in patients with Illness anxiety disorders (IADs). We observed significantly reduced FC between the left extrastriate body area (EBA) and the paracentral lobule compared to healthy controls. Moreover, the correlation analysis between behavioural questionnaires and ROI to ROI FC showed that higher levels of illness anxiety were related to hyper-connectivity between EBA and amygdala and hippocampus. Scores on a questionnaire for interoceptive awareness were significantly correlated with higher FC between right hippocampus and nucleus accumbens bilaterally, and with higher connectivity between left anterior cingulate cortex (ACC) and left orbitofrontal cortex (OFC). Last, patients showed increased interoceptive awareness, measured by Self-Awareness Questionnaire (SAQ), and reduced capability in recognizing emotions, indicating inverse correlation between interoception and emotional awareness. Taken together our results suggested that, in absence of structural and micro-structural changes, patients with IADs show functional alteration in the neural network involved in the self-body representation; such functional alteration might be the target of possible treatments. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Codependency as a mediator between stressful events and eating disorders.

    PubMed

    Meyer, D F

    1997-02-01

    This study examined the role of codependency in the relationship between stressful events and the development of eating disorders. Ninety-five undergraduate women completed the Codependency Assessment, the Eating Disorder Inventory-2, the Differentiation of Self Scale, and an open-ended questionnaire asking about stressful experiences, including relationships with alcoholic family members. Results supported the hypothesis that women who reported experience with an alcoholic significant other or a chronic stressful situation exhibited higher levels of eating disordered behavior. However, a family history of parental alcohol abuse alone did not result in differences in eating disorder symptoms. Further, women who exhibited more characteristics of codependency (e.g., caretaking, needs for control) also evidenced more eating disorder symptoms. The findings suggest a developmental sequence, whereby codependency mediates the relationship between excessive stress and the development of an eating disorder.

  19. Altered resting-state activity in seasonal affective disorder.

    PubMed

    Abou Elseoud, Ahmed; Nissilä, Juuso; Liettu, Anu; Remes, Jukka; Jokelainen, Jari; Takala, Timo; Aunio, Antti; Starck, Tuomo; Nikkinen, Juha; Koponen, Hannu; Zang, Yu-Feng; Tervonen, Osmo; Timonen, Markku; Kiviniemi, Vesa

    2014-01-01

    At present, our knowledge about seasonal affective disorder (SAD) is based mainly up on clinical symptoms, epidemiology, behavioral characteristics and light therapy. Recently developed measures of resting-state functional brain activity might provide neurobiological markers of brain disorders. Studying functional brain activity in SAD could enhance our understanding of its nature and possible treatment strategies. Functional network connectivity (measured using ICA-dual regression), and amplitude of low-frequency fluctuations (ALFF) were measured in 45 antidepressant-free patients (39.78 ± 10.64, 30 ♀, 15 ♂) diagnosed with SAD and compared with age-, gender- and ethnicity-matched healthy controls (HCs) using resting-state functional magnetic resonance imaging. After correcting for Type 1 error at high model orders (inter-RSN correction), SAD patients showed significantly increased functional connectivity in 11 of the 47 identified RSNs. Increased functional connectivity involved RSNs such as visual, sensorimotor, and attentional networks. Moreover, our results revealed that SAD patients compared with HCs showed significant higher ALFF in the visual and right sensorimotor cortex. Abnormally altered functional activity detected in SAD supports previously reported attentional and psychomotor symptoms in patients suffering from SAD. Further studies, particularly under task conditions, are needed in order to specifically investigate cognitive deficits in SAD. Copyright © 2012 Wiley Periodicals, Inc.

  20. Oxytocin and autistic disorder: alterations in peptide forms.

    PubMed

    Green, L; Fein, D; Modahl, C; Feinstein, C; Waterhouse, L; Morris, M

    2001-10-15

    Oxytocin (OT) is synthesized as a prohormone that is sequentially processed to peptides. These peptides are the bioactive amidated form (OT) and the C-terminal extended peptides, OT-Gly, OT-Gly-Lys and OT-Gly-Lys-Arg, which are designated together as OT-X. As an extension of our previous study finding decreased plasma OT in autism, studies were conducted to determine whether there were changes in OT peptide forms in autistic children. Twenty eight male subjects (97 +/- 20 months; range, 70-139 months), diagnosed with DSM-IV autistic disorder through observation and semi-structured interview, were compared with 31 age-matched nonpsychiatric control subjects (106 +/- 22 months; range, 74-140 months). Using OT antisera with different specificity for the peptide forms, we measured plasma OT and OT-X in each group. T tests showed that there was a decrease in plasma OT (t = 4.4, p <.0001), an increase in OT-X (t = 2.3, p <.03) and an increase in the ratio of OT-X/OT (t = 4.5, p <.0001) in the autistic sample, compared with control subjects. The results suggest that children with autistic disorder show alterations in the endocrine OT system. Deficits in OT peptide processing in children with autism may be important in the development of this syndrome.

  1. Alteration of cortico-limbic-striatal neural system in major depressive disorder and bipolar disorder.

    PubMed

    Jiang, Xiaowei; Dai, Xu; Kale Edmiston, Elliot; Zhou, Qian; Xu, Ke; Zhou, Yifang; Wu, Feng; Kong, Lingtao; Wei, Shengnan; Zhou, Yuning; Chang, Miao; Geng, Haiyang; Wang, Dahai; Wang, Ye; Cui, Wenhui; Wang, Fei; Tang, Yanqing

    2017-10-15

    It is often difficult to differentiate major depressive disorder (MDD) and bipolar disorder (BD) merely according to clinical symptoms. Similarities and differences in neural activity between the two disorders remain unclear. In current study, we use amplitude of low-frequency fluctuations (ALFF) to compare neural activation changes between MDD and BD patients. One hundred and eighty-three adolescents and young adults (57 MDD, 46 BD and 80 healthy controls, HC) were scanned during resting state. The ALFF for each participant was calculated, and were then compared among all groups using voxel-based analysis. There was a significant effect of diagnosis in the core regions of cortico-limbic-striatal neural system. Furthermore, MDD showed left-sided abnormal neural activity while BD showed a bilateral abnormality in this neural system. This study was underpowered to consider medications, mood states and neural developmental effects on the neural activation. Differences in lateralization of ALFF alterations were found. Alterations predominated in the left hemisphere for MDD, whereas alterations were bilateral for BD. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Biomarkers of Risk for Post-Traumatic Stress Disorder (PTSD)

    DTIC Science & Technology

    2008-05-01

    McDougle, C.J., Tyrka, A.R., Epperson, C.N., Price, L.H. Cerebrospinal fluid interleukin (IL)-6 in obsessive - compulsive disorder and...Stress Disorder (PTSD) PRINCIPAL INVESTIGATOR: Audrey R. Tyrka, M.D., Ph.D. CONTRACTING ORGANIZATION: Butler Hospital...Stress Disorder (PTSD) 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-07-1-0269 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Audrey R. Tyrka

  3. Longitudinal Associations Among Posttraumatic Stress Disorder, Disordered Eating, and Weight Gain in Military Men and Women

    DTIC Science & Technology

    2016-06-09

    cutting down, annoyance by criticism, guilty feeling, and eye-openers; PTSD, posttraumatic stress disorder . a Persons with missing data for...Abbreviations: CAGE, cutting down, annoyance by criticism, guilty feeling, and eye-openers; PTSD, posttraumatic stress disorder . a Persons with...3.00 (0.43) Abbreviations: CAGE, cutting down, annoyance by criticism, guilty feeling, and eye-openers; PTSD, posttraumatic stress disorder . a Persons

  4. Validating the Primary Care Posttraumatic Stress Disorder Screen and the Posttraumatic Stress Disorder Checklist with Soldiers Returning from Combat

    ERIC Educational Resources Information Center

    Bliese, Paul D.; Wright, Kathleen M.; Adler, Amy B.; Cabrera, Oscar; Castro, Carl A.; Hoge, Charles W.

    2008-01-01

    The purpose of the research was to assess the diagnostic efficiency of the Primary Care Posttraumatic Stress Disorder Screen (PC-PTSD) and the Posttraumatic Stress Disorder Checklist (PCL) as clinical screening tools for active duty soldiers recently returned from a combat deployment. A secondary goal was to examine the item-level characteristics…

  5. Traumatic stress, oxidative stress and posttraumatic stress disorder: neurodegeneration and the accelerated-aging hypothesis

    PubMed Central

    Miller, Mark W.; Sadeh, Naomi

    2014-01-01

    Posttraumatic stress disorder (PTSD) is associated with elevated risk for a variety of age-related diseases and neurodegeneration. In this paper, we review evidence relevant to the hypothesis that chronic PTSD constitutes a form of persistent life stress that potentiates oxidative stress (OXS) and accelerates cellular aging. We provide an overview of empirical studies that have examined the effects of psychological stress on OXS, discuss the stress-perpetuating characteristics of PTSD, and then identify mechanisms by which PTSD might promote OXS and accelerated aging. We review studies on OXS-related genes and the role that they may play in moderating the effects of PTSD on neural integrity and conclude with a discussion of directions for future research on antioxidant treatments and biomarkers of accelerated aging in PTSD. PMID:25245500

  6. Cognitive disruptions in stress-related psychiatric disorders: A role for corticotropin releasing factor (CRF).

    PubMed

    Bangasser, Debra A; Kawasumi, Yushi

    2015-11-01

    This article is part of a Special Issue "SBN 2014". Stress is a potential etiology contributor to both post-traumatic stress disorders (PTSD) and major depression. One stress-related neuropeptide that is hypersecreted in these disorders is corticotropin releasing factor (CRF). Dysregulation of CRF has long been linked to the emotion and mood symptoms that characterize PTSD and depression. However, the idea that CRF also mediates the cognitive disruptions observed in patients with these disorders has received less attention. Here we review literature indicating that CRF can alter cognitive functions. Detailed are anatomical studies revealing that CRF is poised to modulate regions required for learning and memory. We also describe preclinical behavioral studies that demonstrate CRF's ability to alter fear conditioning, impair memory consolidation, and alter a number of executive functions, including attention and cognitive flexibility. The implications of these findings for the etiology and treatment of the cognitive impairments observed in stress-related psychiatric disorders are described. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Post-traumatic stress disorder: facts and fiction.

    PubMed

    Zohar, Joseph; Juven-Wetzler, Alzbeta; Myers, Vicki; Fostick, Leah

    2008-01-01

    This review provides an update on contemporary perspectives on post-traumatic stress disorder and challenges myths about the disorder and its treatment. Post-traumatic stress disorder has recently attracted public attention because of the impact of international terrorism, although the vast majority of post-traumatic stress disorder cases actually relate to civilian events such as car accidents, rape and violent robbery. This disorder requires deeper understanding and consensus among professionals. Advances have been made in elucidating the neurobiology of this disorder, partly by using an animal model of post-traumatic stress disorder. Recent studies have focused on memory processes and the therapeutic role played by plasticity of the hypothalamic-pituitary-adrenal axis, and how this fits (or does not fit) in with the current therapeutic interventions. Guidelines have been established by various bodies in an attempt to streamline treatment options. Understanding of post-traumatic stress disorder is incomplete. Future research should attempt to determine what treatments given during the 'window of opportunity' - the time from exposure until post-traumatic stress disorder develops - are effective. Care should be taken not to interfere with spontaneous recovery.

  8. Paternal stress exposure alters sperm microRNA content and reprograms offspring HPA stress axis regulation

    PubMed Central

    Rodgers, Ali B.; Morgan, Christopher P.; Bronson, Stefanie L.; Revello, Sonia; Bale, Tracy L.

    2013-01-01

    Neuropsychiatric disease frequently presents with an underlying hypo- or hyper- reactivity of the HPA stress axis, suggesting an exceptional vulnerability of this circuitry to external perturbations. Parental lifetime exposures to environmental challenges are associated with increased offspring neuropsychiatric disease risk, and likely contribute to stress dysregulation. While maternal influences have been extensively examined, much less is known regarding the specific role of paternal factors. To investigate the potential mechanisms by which paternal stress may contribute to offspring hypothalamic-pituitary-adrenal (HPA) axis dysregulation, we exposed mice to six weeks of chronic stress prior to breeding. As epidemiological studies support variation in paternal germ cell susceptibility to reprogramming across the lifespan, male stress exposure occurred either throughout puberty or in adulthood. Remarkably, offspring of sires from both paternal stress groups displayed significantly reduced HPA axis stress responsivity. Gene set enrichment analyses in offspring stress regulating brain regions, the paraventricular nucleus (PVN) and the bed nucleus of stria terminalis (BNST), revealed global pattern changes in transcription suggestive of epigenetic reprogramming and consistent with altered offspring stress responsivity, including increased expression of glucocorticoid-responsive genes in the PVN. In examining potential epigenetic mechanisms of germ cell transmission, we found robust changes in sperm miRNA (miR) content, where nine specific miRs were significantly increased in both paternal stress groups. Overall, these results demonstrate that paternal experience across the lifespan can induce germ cell epigenetic reprogramming and impact offspring HPA stress axis regulation, and may therefore offer novel insight into factors influencing neuropsychiatric disease risk. PMID:23699511

  9. Lower electrodermal activity to acute stress in caregivers of people with autism spectrum disorder: an adaptive habituation to stress.

    PubMed

    Ruiz-Robledillo, Nicolás; Moya-Albiol, Luis

    2015-02-01

    Caring for a relative with autism spectrum disorder (ASD) entails being under chronic stress that could alter body homeostasis. Electrodermal activity (EDA) is an index of the sympathetic activity of the autonomic nervous system related to emotionality and homeostasis. This study compares EDA in response to acute stress in the laboratory between parents of people with (n = 30) and without (n = 34) ASD (caregivers and non-caregivers, respectively). Caregivers showed lower EDA in response to acute stress than non-caregivers. They also presented higher trait anxiety, anger, depression, and somatic symptoms than non-caregivers. Higher EDA was related to a worse mood and more severe somatic symptoms only in caregivers. These results could reflect an adaptive habituation to stress and establish that high EDA in response to acute stress depends on caregivers' health.

  10. Smaller stress-sensitive hippocampal subfields in women with borderline personality disorder without posttraumatic stress disorder

    PubMed Central

    Bøen, Erlend; Westlye, Lars T.; Elvsåshagen, Torbjørn; Hummelen, Benjamin; Hol, Per K.; Boye, Birgitte; Andersson, Stein; Karterud, Sigmund; Malt, Ulrik F.

    2014-01-01

    Background Animal and human studies have suggested that hippocampal subfields are differentially vulnerable to stress, but subfield volume has not been investigated in patients with borderline personality disorder (BPD). Based on the putative role of stressful life events as vulnerability factors for BPD, we hypothesized that patients with BPD would exhibit reduced volumes for the stress-sensitive dentate gyrus (DG) and the cornu ammonis (CA) 3 subfields volumes, and that these volumes would be associated with traumatic childhood experiences. Methods All participants underwent 3 T magnetic resonance imaging. Hippocampal subfield volumes were estimated using an automated and validated segmentation algorithm implemented in FreeSurfer. Age and total subcortical grey matter volume were covariates. We assessed traumatic childhood experiences using the Childhood Trauma Questionnaire (CTQ). Results A total of 18 women with BPD and 21 healthy control women were included in the study. Only 1 patient had comorbid posttraumatic stress disorder (PTSD). The volumes of the left (p = 0.005) and right (p = 0.011) DG-CA4 and left (p = 0.007) and right (p = 0.005) CA2–3 subfields were significantly reduced in patients compared with controls. We also found significant group differences for the left (p = 0.032) and right (p = 0.028) CA1, but not for other hippocampal subfields. No associations were found between CTQ scores and subfield volumes. Limitations The self-reported CTQ might be inferior to more comprehensive assessments of traumatic experiences. The sample size was moderate. Conclusion The volumes of stress-sensitive hippocampal subfields are reduced in women with BPD without PTSD. However, the degree to which childhood trauma is responsible for these changes is unclear. PMID:24309162

  11. Altered oxidative stress and carbohydrate metabolism in canine mammary tumors

    PubMed Central

    Jayasri, K.; Padmaja, K.; Saibaba, M.

    2016-01-01

    Aim: Mammary tumors are the most prevalent type of neoplasms in canines. Even though cancer induced metabolic alterations are well established, the clinical data describing the metabolic profiles of animal tumors is not available. Hence, our present investigation was carried out with the aim of studying changes in carbohydrate metabolism along with the level of oxidative stress in canine mammary tumors. Materials and Methods: Fresh mammary tumor tissues along with the adjacent healthy tissues were collected from the college surgical ward. The levels of thiobarbituric acid reactive substances (TBARS), glutathione, protein, hexose, hexokinase, glucose-6-phosphatase, fructose-1, 6-bisphosphatase, and glucose-6-phosphate dehydrogenase (G6PD) were analyzed in all the tissues. The results were analyzed statistically. Results: More than two-fold increase in TBARS and three-fold increase in glutathione levels were observed in neoplastic tissues. Hexokinase activity and hexose concentration (175%) was found to be increased, whereas glucose-6-phosphatase (33%), fructose-1, 6-bisphosphatase (42%), and G6PD (5 fold) activities were reduced in tumor mass compared to control. Conclusion: Finally, it was revealed that lipid peroxidation was increased with differentially altered carbohydrate metabolism in canine mammary tumors. PMID:28096627

  12. Parents of adolescents with psychiatric disorders: insight into the disorder, self-stigma and parental stress.

    PubMed

    Hasson-Ohayon, Ilanit; Tuval-Mashiach, Rivka; Morag-Yaffe, Mayad; Gaziel, Meyrav; Schapir, Lior; Zalsman, Gil; Shoval, Gal

    2014-07-01

    Parents of adolescents with mental disorders experience stress partially due to the way they perceive and experience their offspring's disorder. The current study assessed the mediator role of self-stigma in the relationship between insight into the disorder and parental stress of parents of adolescents with mental disorders. A total of 37 parents of adolescents with psychiatric disorders were assessed for their level of insight, self-stigma and parental stress. The hypothesized mediation model was confirmed and is consistent with previous study on parents of adults with severe mental illness. The positive association between insight and parental stress is mediated by these parents' self-stigma, suggesting that insight increases the self-stigma, which in turn increases the parental stress. These results may have clinical implications with regard to the treatment of the family of adolescents with mental disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Prostitution, violence, and posttraumatic stress disorder.

    PubMed

    Farley, M; Barkan, H

    1998-01-01

    One hundred and thirty people working as prostitutes in San Francisco were interviewed regarding the extent of violence in their lives and symptoms of posttraumatic stress disorder (PTSD). Fifty-seven percent reported that they had been sexually assaulted as children and 49% reported that they had been physically assaulted as children. As adults in prostitution, 82% had been physically assaulted; 83% had been threatened with a weapon; 68% had been raped while working as prostitutes; and 84% reported current or past homelessness. We differentiated the types of lifetime violence as childhood sexual assault; childhood physical abuse; rape in prostitution; and other (non-rape) physical assault in prostitution. PTSD severity was significantly associated with the total number of types of lifetime violence (r = .21, p = .02); with childhood physical abuse (t = 2.97, p = .004); rape in adult prostitution (Student's t = 2.77, p = .01); and the total number of times raped in prostitution (Kruskal-Wallace chi square = 13.51, p = .01). Of the 130 people interviewed, 68% met DSM III-R criteria for a diagnosis of PTSD. Eighty-eight percent of these respondents stated that they wanted to leave prostitution, and described what they needed in order to escape.

  14. Posttraumatic stress disorder and completed suicide.

    PubMed

    Gradus, Jaimie L; Qin, Ping; Lincoln, Alisa K; Miller, Matthew; Lawler, Elizabeth; Sørensen, Henrik Toft; Lash, Timothy L

    2010-03-15

    Most research regarding posttraumatic stress disorder (PTSD) and suicide has focused on suicidal ideation or attempts; no known study of the association between PTSD and completed suicide in a population-based sample has been reported. This study examined the association between PTSD and completed suicide in a population-based sample. Data were obtained from the nationwide Danish health and administrative registries, which include data on all 5.4 million residents of Denmark. All suicides between January 1, 1994, and December 31, 2006, were included, and controls were selected from a sample of all Danish residents. Using this nested case-control design, the authors examined 9,612 suicide cases and 199,306 controls matched to cases on gender, date of birth, and time. Thirty-eight suicide cases (0.40%) and 95 controls (0.05%) were diagnosed with PTSD. The odds ratio associating PTSD with suicide was 9.8 (95% confidence interval: 6.7, 15). The association between PTSD and completed suicide remained after controlling for psychiatric and demographic confounders (odds ratio = 5.3, 95% confidence interval: 3.4, 8.1). Additionally, persons with PTSD and depression had a greater rate of suicide than expected based on their independent effects. In conclusion, a registry-based diagnosis of PTSD based on International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, is a risk factor for completed suicide.

  15. Visual false memories in posttraumatic stress disorder.

    PubMed

    Moradi, Ali Reza; Heydari, Ali Hosain; Abdollahi, Mohammad Hossain; Rahimi-Movaghar, Vafa; Dalgleish, Tim; Jobson, Laura

    2015-11-01

    This study investigated visual false memories in posttraumatic stress disorder (PTSD). The Scenic False Memory paradigm (SFM, Hauschildt, Peters, Jelinek, & Moritz, 2012) was administered to male Iranian military personnel who had participated in the Iran-Iraq war and were diagnosed with (n = 21) or without (n = 21) PTSD and a sample of healthy male non-trauma-exposed controls (n = 21). Trauma-exposed participants recalled and recognized a significantly lower percentage of hits and a significantly greater percentage of false memories for both trauma-related and non-trauma-related video scenes, than non-trauma-exposed controls. Among the trauma-exposed participants, those with and without PTSD did not differ significantly in terms of percentage of hits and false memories recalled on the SFM. Those with PTSD were found to recognize significantly fewer hits for both the trauma-related and non-trauma-related videos than those without PTSD. Those with PTSD also recognized significantly more false memories for the trauma video scene than the non-PTSD group. The findings suggest that those with trauma exposure, and in particular those with PTSD, may have a greater susceptibility to visual false memory.

  16. Posttraumatic stress disorder in former 'comfort women'.

    PubMed

    Min, Sung Kil; Lee, Chang Ho; Kim, Joo Young; Sim, Eun Ji

    2011-01-01

    This study investigated the mental health of former 'comfort women' who serviced the Japanese Imperial Military during the Second World War. We evaluated 26 former comfort women's life histories, cognitive functioning, DSM-IV diagnosis of posttraumatic stress disorder (PTSD), depression, paranoid state, anger, and Rorschach test results, and compared the data with those of 24 healthy women. Cognitive functioning was not significantly different between former comfort women and the comparison group. All 26 former comfort women had undergone traumatic experiences such as sexual slavery and had suffered PTSD symptoms at least once in their lives. Of the 26, 8 (30.8%) were diagnosed as having PTSD, as opposed to none in the comparison group. The women's PTSD symptoms were characterized by avoidance behavior, intrusive and distressing recollections, and anger. There were no significant differences in depression or paranoid state between the two groups, but former comfort women had impairments in anger control. Former comfort women with PTSD were more depressed. On the Rorschach test, former comfort women revealed characteristic responses related not only to sex and morbidity but also to anger and violence. The small number of subjects might not represent all former comfort women. Some data collected by self report might limit the objectivity of the results. The results suggest that former comfort women are still suffering from traumatic memories, symptoms of PTSD, including avoidant behavior, and anger control impairment, even 60 years after the end of the war.

  17. Executive function in cancer patients with posttraumatic stress disorder.

    PubMed

    Yang, Juan; Guo, Juncheng; Jiang, Xiangling

    2017-03-01

    Background Cancer patients with posttraumatic stress disorder can lead to their noncompliant behaviors. However, less is known about the neurocognitive functioning of posttraumatic stress disorder in general cancer types or patient populations. The current study attempted to examine the prevalence of posttraumatic stress disorder and their relationships with executive function in individuals with cancer. Methods A total of 285 cancer patients with posttraumatic stress disorder and 150 healthy individuals were recruited for the present study. The Clinician Administered PTSD Scale, Tower of Hanoi, Wisconsin Card Sorting Test, and Wechsler Adult Intelligence Scale-Revised Chinese revision were administered to all participants. Results Significant differences in the score of Tower of Hanoi, Wisconsin Card Sorting Test, and Wechsler Adult Intelligence Scale-Revised Chinese revision were observed between the posttraumatic stress disorder group and the healthy control group ( p < 0.001). Significant correlations were found between all posttraumatic stress disorder symptoms and executive function. Conclusions These findings suggest that individuals with cancer-related posttraumatic stress disorder exhibit more severe impairment in executive function than healthy controls do.

  18. A biological measure of stress levels in patients with functional movement disorders.

    PubMed

    Maurer, Carine W; LaFaver, Kathrin; Ameli, Rezvan; Toledo, Ryan; Hallett, Mark

    2015-09-01

    While the presence of co-existing psychological stressors has historically been used as a supportive factor in the diagnosis of functional neurological disorders, many patients with functional neurological disorders deny the presence of these stressors. The stress response circuitry in these patients remains largely unexplored. We performed an observational study examining biological stress levels in patients with functional movement disorders as compared with matched healthy controls. Specifically, we compared levels of circulating cortisol, the end-product of the hypothalamic-pituitary-adrenal axis. Salivary cortisol samples were collected from patients with "clinically definite" functional movement disorders (n = 33) and their age- and sex-matched controls (n = 33). Collections were performed at five standardized time points, reflecting participants' diurnal cortisol cycles. To rule out confounders, participants also underwent extensive psychological assessment including Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Hamilton Anxiety Rating Scale, and Hamilton Rating Scale for Depression. Patients with functional movement disorders did not differ from matched controls with respect to levels of circulating cortisol. We demonstrate that current stress levels are not altered in patients with functional movement disorders. Our results warrant careful review of current management of patients with functional neurological symptoms, and suggest that the insistence on heightened stress levels in these patients is unjustified. Published by Elsevier Ltd.

  19. Neurobiological Indicators of Disinhibition in Posttraumatic Stress Disorder

    PubMed Central

    Sadeh, Naomi; Spielberg, Jeffrey M.; Miller, Mark W.; Milberg, William P.; Salat, David H.; Amick, Melissa M.; Fortier, Catherine B.; McGlinchey, Regina E.

    2015-01-01

    Deficits in impulse control are increasingly recognized in association with posttraumatic stress disorder (PTSD). To further our understanding of the neurobiology of PTSD-related disinhibition, we examined alterations in brain morphology and network connectivity associated with response inhibition failures and PTSD severity. The sample consisted of 189 trauma-exposed Operation Enduring Freedom/Operation Iraqi Freedom veterans (89% male, ages 19–62) presenting with a range of current PTSD severity. Disinhibition was measured using commission errors on a Go/No-Go task with emotional stimuli, and PTSD was assessed using a measure of current symptom severity. Whole-brain vertex-wise analyses of cortical thickness revealed two clusters associated with PTSD-related disinhibition (Monte Carlo cluster corrected p< .05). The first cluster included portions of right inferior and middle frontal gyri and frontal pole. The second cluster spanned portions of left medial orbital frontal, rostral anterior cingulate, and superior frontal gyrus. In both clusters, commission errors were associated with reduced cortical thickness at higher (but not lower) levels of PTSD symptoms. Resting-state fMRI analyses revealed alterations in the functional connectivity of the right frontal cluster. Together, study findings suggest that reductions in cortical thickness in regions involved in flexible decision-making, emotion regulation, and response inhibition contribute to impulse control deficits in PTSD. Further, aberrant coupling between frontal regions and networks involved in selective attention, memory/learning, and response preparation suggest disruptions in functional connectivity may also play a role. PMID:25959594

  20. Management of post traumatic stress disorder using combat stress treatment principles--a case report.

    PubMed

    Lee, J T

    1997-01-01

    Combat stress casualties are only generated by war. However, military psychiatrists need to acquire the experience and skills that they would need before they are ever faced with their first combat stress casualty. Non-combat post traumatic stress disorder patients present the best approximation to combat stress casualties. This case study demonstrates how combat stress treatment principles can be successfully applied to a case of non-combat post traumatic stress disorder patient. It is not the intention of this paper to demonstrate whether the combat stress management protocol is superior to other methods or protocols. Recommendations are made on methods to identify post traumatic stress disorder patients and how to seize every available opportunity to practise combat stress treatment principles.

  1. Alterations in Lipid and Inositol Metabolisms in Two Dopaminergic Disorders

    PubMed Central

    Berger, Hannah S.; Do, Kieu Trinh; Kastenmüller, Gabi; Wahl, Simone; Adamski, Jerzy; Peters, Annette; Krumsiek, Jan; Suhre, Karsten; Haslinger, Bernhard; Ceballos-Baumann, Andres; Gieger, Christian; Winkelmann, Juliane

    2016-01-01

    Background Serum metabolite profiling can be used to identify pathways involved in the pathogenesis of and potential biomarkers for a given disease. Both restless legs syndrome (RLS) and Parkinson`s disease (PD) represent movement disorders for which currently no blood-based biomarkers are available and whose pathogenesis has not been uncovered conclusively. We performed unbiased serum metabolite profiling in search of signature metabolic changes for both diseases. Methods 456 metabolites were quantified in serum samples of 1272 general population controls belonging to the KORA cohort, 82 PD cases and 95 RLS cases by liquid-phase chromatography and gas chromatography separation coupled with tandem mass spectrometry. Genetically determined metabotypes were calculated using genome-wide genotyping data for the 1272 general population controls. Results After stringent quality control, we identified decreased levels of long-chain (polyunsaturated) fatty acids of individuals with PD compared to both RLS (PD vs. RLS: p = 0.0001 to 5.80x10-9) and general population controls (PD vs. KORA: p = 6.09x10-5 to 3.45x10-32). In RLS, inositol metabolites were increased specifically (RLS vs. KORA: p = 1.35x10-6 to 3.96x10-7). The impact of dopaminergic drugs was reflected in changes in the phenylalanine/tyrosine/dopamine metabolism observed in both individuals with RLS and PD. Conclusions A first discovery approach using serum metabolite profiling in two dopamine-related movement disorders compared to a large general population sample identified significant alterations in the polyunsaturated fatty acid metabolism in PD and implicated the inositol metabolism in RLS. These results provide a starting point for further studies investigating new perspectives on factors involved in the pathogenesis of the two diseases as well as possible points of therapeutic intervention. PMID:26808974

  2. Epigenetic and genetic alterations of the imprinting disorder Beckwith-Wiedemann syndrome and related disorders.

    PubMed

    Soejima, Hidenobu; Higashimoto, Ken

    2013-07-01

    Genomic imprinting is an epigenetic phenomenon that leads to parent-specific differential expression of a subset of genes. Most imprinted genes form clusters, or imprinting domains, and are regulated by imprinting control regions. As imprinted genes have an important role in growth and development, aberrant expression of imprinted genes due to genetic or epigenetic abnormalities is involved in the pathogenesis of human disorders, or imprinting disorders. Beckwith-Wiedemann syndrome (BWS) is a representative imprinting disorder characterized by macrosomia, macroglossia and abdominal wall defects, and exhibits a predisposition to tumorigenesis. The relevant imprinted chromosomal region in BWS is 11p15.5, which consists of two imprinting domains, IGF2/H19 and CDKN1C/KCNQ1OT1. BWS has five known causative epigenetic and genetic alterations: loss of methylation (LOM) at KvDMR1, gain of methylation (GOM) at H19DMR, paternal uniparental disomy, CDKN1C mutations and chromosomal rearrangements. Opposite methylation defects, GOM and LOM, at H19DMR are known to cause clinically opposite disorders: BWS and Silver-Russell syndrome, respectively. Interestingly, a recent study discovered that loss of function or gain of function of CDKN1C also causes clinically opposite disorders, BWS and IMAGe (intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies) syndrome, respectively. Furthermore, several clinical studies have suggested a relationship between assisted reproductive technology (ART) and the risk of imprinting disorders, along with the existence of trans-acting factors that regulate multiple imprinted differentially methylated regions. In this review, we describe the latest knowledge surrounding the imprinting mechanism of 11p15.5, in addition to epigenetic and genetic etiologies of BWS, associated childhood tumors, the effects of ART and multilocus hypomethylation disorders.

  3. Posttraumatic stress disorder in critical illness survivors: a metaanalysis.

    PubMed

    Parker, Ann M; Sricharoenchai, Thiti; Raparla, Sandeep; Schneck, Kyle W; Bienvenu, O Joseph; Needham, Dale M

    2015-05-01

    To conduct a systematic review and metaanalysis of the prevalence, risk factors, and prevention/treatment strategies for posttraumatic stress disorder symptoms in critical illness survivors. PubMed, Embase, CINAHL, PsycINFO, and Cochrane Library from inception through March 5, 2014. Eligible studies met the following criteria: 1) adult general/nonspecialty ICU, 2) validated posttraumatic stress disorder instrument greater than or equal to 1 month post-ICU, and 3) sample size greater than or equal to 10 patients. Duplicate independent review and data abstraction from all eligible titles/abstracts/full-text articles. The search identified 2,817 titles/abstracts, with 40 eligible articles on 36 unique cohorts (n = 4,260 patients). The Impact of Event Scale was the most common posttraumatic stress disorder instrument. Between 1 and 6 months post-ICU (six studies; n = 456), the pooled mean (95% CI) Impact of Event Scale score was 20 (17-24), and the pooled prevalences of clinically important posttraumatic stress disorder symptoms (95% CI) were 25% (18-34%) and 44% (36-52%) using Impact of Event Scale thresholds greater than or equal to 35 and greater than or equal to 20, respectively. Between 7 and 12 months post-ICU (five studies; n = 698), the pooled mean Impact of Event Scale score was 17 (9-24), and pooled prevalences of posttraumatic stress disorder symptoms were 17% (10-26%) and 34% (22-50%), respectively. ICU risk factors for posttraumatic stress disorder symptoms included benzodiazepine administration and post-ICU memories of frightening ICU experiences. Posttraumatic stress disorder symptoms were associated with worse quality of life. In European-based studies: 1) an ICU diary was associated with a significant reduction in posttraumatic stress disorder symptoms, 2) a self-help rehabilitation manual was associated with significant posttraumatic stress disorder symptom reduction at 2 months, but not 6 months; and 3) a nurse-led ICU follow-up clinic did not reduce

  4. The relationship between acculturative stress and eating disorder symptoms: is it unique from general life stress?

    PubMed

    Kroon Van Diest, Ashley M; Tartakovsky, Margarita; Stachon, Caitlin; Pettit, Jeremy W; Perez, Marisol

    2014-06-01

    The purpose of the current study was to expand upon the literature examining the relationship between acculturative stress and eating disorder symptoms among different ethnic groups. Specifically, acculturative stress was explored as a moderator of the relationship between body dissatisfaction and eating disorder symptoms among ethnic minority women. Additionally, the distinction between acculturative stress and general life stress in predicting eating disorder symptoms was assessed. Participants consisted of 247 undergraduate women, all of whom were members of an ethnic minority group including African Americans, Asian Americans, and Latinas. Acculturative stress was found to moderate the relationship between body dissatisfaction and eating disorder symptoms, but only among African American women. Acculturative stress was also found to significantly predict bulimic symptoms above and beyond general life stress among African American, Asian American, and Latina women.

  5. Altered lipid metabolism in brain injury and disorders.

    PubMed

    Adibhatla, Rao Muralikrishna; Hatcher, J F

    2008-01-01

    Deregulated lipid metabolism may be of particular importance for CNS injuries and disorders, as this organ has the highest lipid concentration next to adipose tissue. Atherosclerosis (a risk factor for ischemic stroke) results from accumulation of LDL-derived lipids in the arterial wall. Pro-inflammatory cytokines (TNF-alpha and IL-1), secretory phospholipase A2 IIA and lipoprotein-PLA2 are implicated in vascular inflammation. These inflammatory responses promote atherosclerotic plaques, formation and release of the blood clot that can induce ischemic stroke. TNF-alpha and IL-1 alter lipid metabolism and stimulate production of eicosanoids, ceramide, and reactive oxygen species that potentiate CNS injuries and certain neurological disorders. Cholesterol is an important regulator of lipid organization and the precursor for neurosteroid biosynthesis. Low levels of neurosteroids were related to poor outcome in many brain pathologies. Apolipoprotein E is the principal cholesterol carrier protein in the brain, and the gene encoding the variant Apolipoprotein E4 is a significant risk factor for Alzheimer's disease. Parkinson's disease is to some degree caused by lipid peroxidation due to phospholipases activation. Niemann-Pick diseases A and B are due to acidic sphingomyelinase deficiency, resulting in sphingomyelin accumulation, while Niemann-Pick disease C is due to mutations in either the NPC1 or NPC2 genes, resulting in defective cholesterol transport and cholesterol accumulation. Multiple sclerosis is an autoimmune inflammatory demyelinating condition of the CNS. Inhibiting phospholipase A2 attenuated the onset and progression of experimental autoimmune encephalomyelitis. The endocannabinoid system is hypoactive in Huntington's disease. Ethyl-eicosapetaenoate showed promise in clinical trials. Amyotrophic lateral sclerosis causes loss of motorneurons. Cyclooxygenase-2 inhibition reduced spinal neurodegeneration in amyotrophic lateral sclerosis transgenic mice

  6. The Impact of Neuroimmune Alterations in Autism Spectrum Disorder

    PubMed Central

    Gottfried, Carmem; Bambini-Junior, Victorio; Francis, Fiona; Riesgo, Rudimar; Savino, Wilson

    2015-01-01

    Autism spectrum disorder (ASD) involves a complex interplay of both genetic and environmental risk factors, with immune alterations and synaptic connection deficiency in early life. In the past decade, studies of ASD have substantially increased, in both humans and animal models. Immunological imbalance (including autoimmunity) has been proposed as a major etiological component in ASD, taking into account increased levels of pro-inflammatory cytokines observed in postmortem brain from patients, as well as autoantibody production. Also, epidemiological studies have established a correlation of ASD with family history of autoimmune diseases; associations with major histocompatibility complex haplotypes and abnormal levels of immunological markers in the blood. Moreover, the use of animal models to study ASD is providing increasing information on the relationship between the immune system and the pathophysiology of ASD. Herein, we will discuss the accumulating literature for ASD, giving special attention to the relevant aspects of factors that may be related to the neuroimmune interface in the development of ASD, including changes in neuroplasticity. PMID:26441683

  7. Chronic stress effects in contralateral medial pterygoid muscle of rats with occlusion alteration.

    PubMed

    Loyola, Bruno Melo; Nascimento, Glauce Crivelaro; Fernández, Rodrigo Alberto Restrepo; Iyomasa, Daniela Mizusaki; Pereira, Yamba Carla Lara; Leite-Panissi, Christie Ramos Andrade; Issa, João Paulo Mardegan; Iyomasa, Mamie Mizusaki

    2016-10-01

    Temporomandibular disorder (TMD) has a high prevalence in our society, characterized by a severe pain condition of the masticatory muscles and temporomandibular joint. Despite the indication of multiple factor initiators of TMD, there is still controversy about its etiology and its pathophysiology is poorly understood. Using rats as experimental animals we investigated the effect of unpredictable chronic stress with or without unilateral molar extraction on the contralateral medial pterygoid muscle. Our hypothesis is that these two factors induce changes in morphology, oxidative metabolism and oxidative stress of muscle fibers. Young adult male Wistar rats (±200g) were divided into four groups: a group with extraction and unpredictable chronic stress (E+US); with extraction and without stress (E+C); without extraction and with unpredictable chronic stress (NO+US); and a control group without either extraction or stress (NO+C). The animals were subjected to unilateral extraction of the upper left molars, under intraperitoneal anesthesia with 4% Xylazine (10mg/kg) and 10% Ketamine (80mg/kg) on day zero. The rats of groups E+US and NO+US were submitted to different protocols of stress, from the 14th day after the extraction. The protocols were different every day for five consecutive days, which were repeated from the 6th day for five days more. Contralateral medial pterygoid muscles were obtained on the 24th day after the start of the experiment for morphological, metabolic, capillary density, and oxidative stress analysis. The data from capillary density showed a decrease of capillaries in animals subjected to dental extraction, compared with those without extraction and an increase of laminin expression in the group submitted to the unpredictable chronic stress when compared to the unexposed to stress. SDH test revealed a decrease of light fibers in the group submitted to unilateral extraction of molars, compared with this area in the control group. In E+US and NO

  8. Interactions between Disordered Sleep, Post-Traumatic Stress Disorder, and Substance Use Disorders

    PubMed Central

    Vandrey, Ryan; Babson, Kimberly A.; Herrmann, Evan S.; Bonn-Miller, Marcel O.

    2014-01-01

    Disordered sleep is associated with a number of adverse health consequences and is an integral component of many psychiatric disorders. Rates of substance use disorders (SUDs) are markedly higher among individuals with posttraumatic stress disorder (PTSD), and this relationship may be partly mediated by disturbed sleep. Sleep disturbances (e.g. insomnia, daytime sleepiness, vivid nightmares) are hallmark features of PTSD and there is evidence that individuals with PTSD engage in substance use as a means of coping with these symptoms. However, prolonged substance use can lead to more severe sleep disturbances due to the development of tolerance and withdrawal. Behavioral or pharmacological treatment of disordered sleep is associated with improved daytime symptoms and psychosocial functioning among individuals who have developed PTSD. Initial research also suggests that improving sleep could be similarly beneficial in reducing coping oriented substance use and preventing relapse among those seeking treatment for SUDs. Together, these findings suggest that ameliorating sleep disturbance among at-risk individuals would be a viable target for the prevention and treatment of PTSD and associated SUDs, but prospective research is needed to examine this hypothesis. Enhanced understanding of the interrelation between sleep, PTSD, and SUDs may yield novel prevention and intervention approaches for these costly, prevalent and frequently co-occurring disorders. PMID:24892898

  9. Enhancing Exposure Therapy for Anxiety Disorders, Obsessive Compulsive Disorder, and Posttraumatic Stress Disorder

    PubMed Central

    McGuire, Joseph F.; Lewin, Adam B.; Storch, Eric A.

    2014-01-01

    Translating findings from basic science, several compounds have been identified that may enhance therapeutic outcomes and/or expedite treatment gains when administered alongside exposure-based treatments. Four of these compounds (referred to as cognitive enhancers) have been evaluated in the context of randomized controlled trials for anxiety disorders (e.g., specific phobias, panic disorder, social anxiety disorder), obsessive compulsive disorder (OCD), and posttraumatic stress disorder (PTSD). These cognitive enhancers include D-cycloserine, yohimbine hydrochloride, glucocorticoids and cortisol, and brain derived neurotrophic factor. There is consistent evidence that cognitive enhancers can enhance therapeutic outcomes and/or expedite treatment gains across anxiety disorders, OCD, and PTSD. Emerging evidence has highlighted the importance of within-session fear habituation and between-session fear learning, which can either enhance fear extinction or reconsolidate of fear responses. Although findings from these trials are promising, there are several considerations that warrant further evaluation prior to wide-spread use of cognitive enhancers in exposure-based treatments. Consistent trial design and large sample sizes are important in future studies of cognitive enhancers. PMID:24972729

  10. Prevalence and predictors of stress disorders following two earthquakes.

    PubMed

    Yuan, Kang Chuan; Ruo Yao, Zhao; Zhen Yu, Shi; Xu Dong, Zhao; Jian Zhong, Yang; Edwards, Jason Glen; Edwards, Glen David

    2013-09-01

    Studies about stress disorders following a disaster have mainly been based on single-event trauma with little emphasis on multiple traumas. This study investigated the prevalence and predictors of stress disorders following two earthquakes in China. Subjects were randomly sampled from 11 villages in rural China. A total of 624 subjects were administered with the 12-item General Health Questionnaire (GHQ-12), Symptom Checklist -90-R (SCL-90-R), Coping Style Scale and Social Support Rating Scale. This was followed by a structural clinical interview using the Chinese translation of the Structured Clinical Interview for Diagnostic and Statistical Manual (DSM)-IV-TR axis 1 disorders (SCID-I-P) for acute stress disorder (ASD) and post-traumatic stress disorder (PTSD). The prevalence of ASD and PTSD was 15% and 29%, respectively. Regression analysis indicated that high intensity of trauma exposure, lower educational level, subjective feeling of economic status and psychological stress after the first earthquake significantly predicted the outcome of PTSD. The study suggested that the prevalence of stress disorders in two earthquakes were higher than that experienced in a single disaster. The intensity of trauma exposure, low educational level, bad subjective feeling of economic status, and psychological stress after the first earthquake could be used to identify survivors at risk of developing PTSD in two earthquakes.

  11. Interaction of Metabolic Stress with Chronic Mild Stress in Altering Brain Cytokines and Sucrose Preference

    PubMed Central

    Remus, Jennifer L.; Stewart, Luke T.; Camp, Robert M.; Novak, Colleen M.; Johnson, John D.

    2015-01-01

    There is growing evidence that metabolic stressors increase an organism’s risk of depression. Chronic mild stress is a popular animal model of depression and several serendipitous findings have suggested that food deprivation prior to sucrose testing in this model is necessary to observe anhedonic behaviors. Here, we directly tested this hypothesis by exposing animals to chronic mild stress and used an overnight two bottle sucrose test (food ad libitum) on day 5 and 10, then food and water deprive animals overnight and tested their sucrose consumption and preference in a 1h sucrose test the following morning. Approximately 65% of stressed animals consumed sucrose and showed a sucrose preference similar to non-stressed controls in an overnight sucrose test, while 35% showed a decrease in sucrose intake and preference. Following overnight food and water deprivation the previously ‘resilient’ animals showed a significant decrease in sucrose preference and greatly reduced sucrose intake. In addition, we evaluated whether the onset of anhedonia following food and water deprivation corresponds to alterations in corticosterone, epinephrine, circulating glucose, or interleukin-1 beta expression in limbic brain areas. While all stressed animals showed adrenal hypertrophy and elevated circulating epinephrine, only stressed animals that were food deprived were hypoglycemic compared to food deprived controls. Additionally, food and water deprivation significantly increased hippocampus IL-1β while food and water deprivation only increased hypothalamus IL-1β in stress susceptible animals. These data demonstrate that metabolic stress of food and water deprivation interacts with chronic stressor exposure to induce physiological and anhedonic responses. PMID:25914924

  12. Does heat stress alter the pig's response to dietary fat?

    PubMed

    Kellner, T A; Baumgard, L H; Prusa, K J; Gabler, N K; Patience, J F

    2016-11-01

    PFTN; = 0.624). Jowl IV at market increased with increasing degree of unsaturation of the dietary fat (68.5 g/100 g for CNTR, 68.2 g/100 g for TAL, and 71.5 g/100 g for CO; < 0.001). Heat stress decreased mRNA abundance of and ( ≤ 0.041). Heat stress and CO increased mRNA abundance of ( ≤ 0.047), and CO increased abundance of ( = 0.011). In conclusion, HS does not alter the pig's response to dietary fat. However, HS leads to reduced ADG, ADFI, G:F, and caloric efficiency and a suppression of mRNA abundance of genes involved in the lipolytic cascade, which resulted in a phenotype that was fatter than PFTN.

  13. Update on the management of post-traumatic stress disorder

    PubMed Central

    Wallace, Duncan; Cooper, John

    2015-01-01

    Summary Post-traumatic stress disorder occurs in people exposed to life-threatening trauma. GPs may be seeing more patients with post-traumatic stress disorder as military personnel return from overseas deployments. The condition can present in various ways. To reduce the likelihood of missed or delayed diagnosis GPs can screen at-risk populations. A comprehensive assessment is recommended. Specialist referral may be required, particularly if there are other mental health problems. Trauma-focused psychological therapies should be offered as the first line of treatment for post-traumatic stress disorder. Usually 8–12 sessions are needed for a therapeutic effect. If drug treatment is needed, selective serotonin reuptake inhibitors are the first line. Other drugs used in post-traumatic stress disorder include antipsychotics, anticonvulsants and prazosin. PMID:26648617

  14. Update on the management of post-traumatic stress disorder.

    PubMed

    Wallace, Duncan; Cooper, John

    2015-04-01

    Post-traumatic stress disorder occurs in people exposed to life-threatening trauma. GPs may be seeing more patients with post-traumatic stress disorder as military personnel return from overseas deployments. The condition can present in various ways. To reduce the likelihood of missed or delayed diagnosis GPs can screen at-risk populations. A comprehensive assessment is recommended. Specialist referral may be required, particularly if there are other mental health problems. Trauma-focused psychological therapies should be offered as the first line of treatment for post-traumatic stress disorder. Usually 8-12 sessions are needed for a therapeutic effect. If drug treatment is needed, selective serotonin reuptake inhibitors are the first line. Other drugs used in post-traumatic stress disorder include antipsychotics, anticonvulsants and prazosin.

  15. Post-Traumatic Stress Disorder in Children: Suggested Intervention.

    ERIC Educational Resources Information Center

    Csapo, Marg

    1991-01-01

    This paper reviews literature-based techniques of intervention with posttraumatic stress disorder in children, including such techniques as crisis intervention, in vitro flooding, communication training, physical mastery, perspective taking, elimination of self-blame, and self-calming. (JDD)

  16. Post-Traumatic Stress Disorder in Children: Suggested Intervention.

    ERIC Educational Resources Information Center

    Csapo, Marg

    1991-01-01

    This paper reviews literature-based techniques of intervention with posttraumatic stress disorder in children, including such techniques as crisis intervention, in vitro flooding, communication training, physical mastery, perspective taking, elimination of self-blame, and self-calming. (JDD)

  17. Predator odor stress alters corticotropin-releasing factor-1 receptor (CRF1R)-dependent behaviors in rats.

    PubMed

    Roltsch, Emily A; Baynes, Brittni B; Mayeux, Jacques P; Whitaker, Annie M; Baiamonte, Brandon A; Gilpin, Nicholas W

    2014-04-01

    Humans with stress-related anxiety disorders exhibit increases in arousal and alcohol drinking, as well as altered pain processing. Our lab has developed a predator odor stress model that produces reliable and lasting increases in alcohol drinking. Here, we utilize this predator odor stress model to examine stress-induced increases in arousal, nociceptive processing, and alcohol self-administration by rats, and also to determine the effects of corticotropin-releasing factor-1 receptors (CRF1Rs) in mediating these behavioral changes. In a series of separate experiments, rats were exposed to predator odor stress, then tested over subsequent days for thermal nociception in the Hargreaves test, acoustic startle reactivity, or operant alcohol self-administration. In each experiment, rats were systemically injected with R121919, a CRF1R antagonist, and/or vehicle. Predator odor stress increased thermal nociception (i.e., hyperalgesia) and acoustic startle reactivity. Systemic administration of R121919 reduced thermal nociception and hyperarousal in stressed rats but not unstressed controls, and reduced operant alcohol responding over days. Stressed rats exhibited increased sensitivity to the behavioral effects of R121919 in all three tests, suggesting up-regulation of brain CRF1Rs number and/or function in stressed rats. These results suggest that post-stress alcohol drinking may be driven by a high-nociception high-arousal state, and that brain CRF1R signaling mediates these stress effects.

  18. Virtual reality exposure therapy for post-traumatic stress disorder and other anxiety disorders.

    PubMed

    Gerardi, Maryrose; Cukor, Judith; Difede, Joann; Rizzo, Albert; Rothbaum, Barbara Olasov

    2010-08-01

    Anxiety disorders, including phobias and post-traumatic stress disorder, are common and disabling disorders that often involve avoidance behavior. Cognitive-behavioral treatments, specifically imaginal and in vivo forms of exposure therapy, have been accepted and successful forms of treatment for these disorders. Virtual reality exposure therapy, an alternative to more traditional exposure-based therapies, involves immersion in a computer-generated virtual environment that minimizes avoidance and facilitates emotional processing. In this article, we review evidence on the application of virtual reality exposure therapy to the treatment of specific phobias and post-traumatic stress disorder and discuss its advantages and cautions.

  19. Maternal Stress in Nonverbal Learning Disorder: A Comparison with Reading Disorder

    ERIC Educational Resources Information Center

    Antshel, Kevin M.; Joseph, Guy-Ronald

    2006-01-01

    Maternal stress was assessed in mothers of children ages 8 to 11 years with learning disorders (LD). Age-, gender-, and IQ-matched children with reading disorders (RD; n = 31), children with nonverbal learning disorders (NVLD; n = 21), and typically developing control participants (n = 23) participated. Mothers of children with LD reported higher…

  20. The physician's role in managing acute stress disorder.

    PubMed

    Kavan, Michael G; Elsasser, Gary N; Barone, Eugene J

    2012-10-01

    Acute stress disorder is a psychiatric diagnosis that may occur in patients within four weeks of a traumatic event. Features include anxiety, intense fear or helplessness, dissociative symptoms, reexperiencing the event, and avoidance behaviors. Persons with this disorder are at increased risk of developing posttraumatic stress disorder. Other risk factors for posttraumatic stress disorder include current or family history of anxiety or mood disorders, a history of sexual or physical abuse, lower cognitive ability, engaging in excessive safety behaviors, and greater symptom severity one to two weeks after the trauma. Common reactions to trauma include physical, mental, and emotional symptoms. Persistent psychological distress that is severe enough to interfere with psychological or social functioning may warrant further evaluation and intervention. Patients experiencing acute stress disorder may benefit from psychological first aid, which includes ensuring the patient's safety; providing information about the event, stress reactions, and how to cope; offering practical assistance; and helping the patient to connect with social support and other services. Cognitive behavior therapy is effective in reducing symptoms and decreasing the future incidence of posttraumatic stress disorder. Critical Incident Stress Debriefing aims to mitigate emotional distress through sharing emotions about the traumatic event, providing education and tips on coping, and attempting to normalize reactions to trauma. However, this method may actually impede natural recovery by overwhelming victims. There is insufficient evidence to recommend the routine use of drugs in the treatment of acute stress disorder. Short-term pharmacologic intervention may be beneficial in relieving specific associated symptoms, such as pain, insomnia, and depression.

  1. Attenuated DHEA and DHEA-S response to acute psychosocial stress in individuals with depressive disorders.

    PubMed

    Jiang, Xiaoling; Zhong, Wen; An, Haiyan; Fu, Mingyu; Chen, Yuanyuan; Zhang, Zhenggang; Xiao, Zhongju

    2017-06-01

    In recent years, a relationship between depression and basal dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) levels has frequently been suggested, but responses of these adrenal steroids to psychosocial stress have not been examined in individuals with depressive disorders. In this study, we examined salivary DHEA, DHEA-S, and cortisol/DHEA response to the Trier Social Stress Test (TSST) in individuals with depressive disorders and in healthy controls to discover whether the responses of DHEA and DHEA-S to acute psychosocial stress could be a more sensitive marker of HPA dysfunction in depressive disorders. We compared salivary cortisol, DHEA, DHEA-S, and cortisol/DHEA levels to the TSST tests between 38 individuals with depression and 43 healthy controls aged 18.4-25.9 years. Depression severity was assessed by the self-reported Beck Depression Inventory-II (BDI-II). Salivary samples were evaluated at four time points: the baseline (-10 time point), before the TSST started (0 time point), the end of the TSST (+20 time point), and the recovery (+50 time points). No significant differences existed in the basal adrenal hormonal levels between subjects with depressive disorders and controls; however, at the end of TSST, attenuated DHEA and DHEA-S response was identified in subjects with depressive disorders compared to that found in healthy subjects. The differences in the DHEA and DHEA-S levels at the +20 time point, as well as the differences in the cortisol/DHEA at the +50 time point, exhibited negative correlations with depression severity. Attenuated DHEA and DHEA-S response to acute psychosocial stress was identified in subjects with depressive disorders. These findings help us to discover the bi-directional relationship between depression and the hypothalamic-pituitary-adrenal (HPA) axis function, hence furthering our understanding of whether altered DHEA and DHEA-S response to psychosocial stress may be a more sensitive method than

  2. Markers of inflammation and stress distinguish subsets of individuals with schizophrenia and bipolar disorder

    PubMed Central

    Fillman, S G; Sinclair, D; Fung, S J; Webster, M J; Shannon Weickert, C

    2014-01-01

    Schizophrenia and bipolar disorder share a number of common features, both symptomatically and biologically. Abnormalities in the neuroimmune and the stress-signaling pathways have been previously identified in brains of individuals with both diseases. However, the possible relationship between abnormalities in stress and neuroimmune signaling within the cortex of people with psychotic illness has not been defined. To test the hypothesis that combined alterations in brain stress responsiveness and neuroimmune/inflammatory status are characteristic of some individuals suffering from major mental illness, we examined gene expression in the Stanley Array Cohort of 35 controls, 35 individuals with schizophrenia and 34 individuals with bipolar disorder. We used levels of 8 inflammatory-related transcripts, of which SERPINA3 was significantly elevated in individuals with schizophrenia (F(2,88)=4.137, P<0.05), and 12 glucocorticoid receptor signaling (stress) pathway transcripts previously examined, to identify two clusters of individuals: a high inflammation/stress group (n=32) and a low (n=68) inflammation/stress group. The high inflammation/stress group has a significantly greater number of individuals with schizophrenia (n=15), and a trend toward having more bipolar disorder individuals (n=11), when compared with controls (n=6). Using these subgroups, we tested which microarray-assessed transcriptional changes may be associated with high inflammatory/stress groups using ingenuity analysis and found that an extended network of gene expression changes involving immune, growth factors, inhibitory signaling and cell death factors also distinguished these groups. Our work demonstrates that some of the heterogeneity in schizophrenia and bipolar disorder may be partially explained by inflammation/stress interactions, and that this biological subtype cuts across Diagnostic and Statistical Manual of Mental Disorders (DSM)-defined categories. PMID:24569695

  3. Markers of inflammation and stress distinguish subsets of individuals with schizophrenia and bipolar disorder.

    PubMed

    Fillman, S G; Sinclair, D; Fung, S J; Webster, M J; Shannon Weickert, C

    2014-02-25

    Schizophrenia and bipolar disorder share a number of common features, both symptomatically and biologically. Abnormalities in the neuroimmune and the stress-signaling pathways have been previously identified in brains of individuals with both diseases. However, the possible relationship between abnormalities in stress and neuroimmune signaling within the cortex of people with psychotic illness has not been defined. To test the hypothesis that combined alterations in brain stress responsiveness and neuroimmune/inflammatory status are characteristic of some individuals suffering from major mental illness, we examined gene expression in the Stanley Array Cohort of 35 controls, 35 individuals with schizophrenia and 34 individuals with bipolar disorder. We used levels of 8 inflammatory-related transcripts, of which SERPINA3 was significantly elevated in individuals with schizophrenia (F(2,88)=4.137, P<0.05), and 12 glucocorticoid receptor signaling (stress) pathway transcripts previously examined, to identify two clusters of individuals: a high inflammation/stress group (n=32) and a low (n=68) inflammation/stress group. The high inflammation/stress group has a significantly greater number of individuals with schizophrenia (n=15), and a trend toward having more bipolar disorder individuals (n=11), when compared with controls (n=6). Using these subgroups, we tested which microarray-assessed transcriptional changes may be associated with high inflammatory/stress groups using ingenuity analysis and found that an extended network of gene expression changes involving immune, growth factors, inhibitory signaling and cell death factors also distinguished these groups. Our work demonstrates that some of the heterogeneity in schizophrenia and bipolar disorder may be partially explained by inflammation/stress interactions, and that this biological subtype cuts across Diagnostic and Statistical Manual of Mental Disorders (DSM)-defined categories.

  4. Stress Transmission and Failure in Disordered Porous Media

    NASA Astrophysics Data System (ADS)

    Laubie, Hadrien; Radjai, Farhang; Pellenq, Roland; Ulm, Franz-Josef

    2017-08-01

    By means of extensive lattice-element simulations, we investigate stress transmission and its relation with failure properties in increasingly disordered porous systems. We observe a non-Gaussian broadening of stress probability density functions under tensile loading with increasing porosity and disorder, revealing a gradual transition from a state governed by single-pore stress concentration to a state controlled by multipore interactions and metric disorder. This effect is captured by the excess kurtosis of stress distributions and shown to be nicely correlated with the second moment of local porosity fluctuations, which appears thus as a (dis)order parameter for the system. By generating statistical ensembles of porous textures with varying porosity and disorder, we derive a general expression for the fracture stress as a decreasing function of porosity and disorder. Focusing on critical sites where the local stress is above the global fracture threshold, we also analyze the transition to failure in terms of a coarse-graining length. These findings provide a general framework which can also be more generally applied to multiphase and structural heterogeneous materials.

  5. Altered Auditory and Multisensory Temporal Processing in Autism Spectrum Disorders

    PubMed Central

    Kwakye, Leslie D.; Foss-Feig, Jennifer H.; Cascio, Carissa J.; Stone, Wendy L.; Wallace, Mark T.

    2011-01-01

    Autism spectrum disorders (ASD) are characterized by deficits in social reciprocity and communication, as well as by repetitive behaviors and restricted interests. Unusual responses to sensory input and disruptions in the processing of both unisensory and multisensory stimuli also have been reported frequently. However, the specific aspects of sensory processing that are disrupted in ASD have yet to be fully elucidated. Recent published work has shown that children with ASD can integrate low-level audiovisual stimuli, but do so over an extended range of time when compared with typically developing (TD) children. However, the possible contributions of altered unisensory temporal processes to the demonstrated changes in multisensory function are yet unknown. In the current study, unisensory temporal acuity was measured by determining individual thresholds on visual and auditory temporal order judgment (TOJ) tasks, and multisensory temporal function was assessed through a cross-modal version of the TOJ task. Whereas no differences in thresholds for the visual TOJ task were seen between children with ASD and TD, thresholds were higher in ASD on the auditory TOJ task, providing preliminary evidence for impairment in auditory temporal processing. On the multisensory TOJ task, children with ASD showed performance improvements over a wider range of temporal intervals than TD children, reinforcing prior work showing an extended temporal window of multisensory integration in ASD. These findings contribute to a better understanding of basic sensory processing differences, which may be critical for understanding more complex social and cognitive deficits in ASD, and ultimately may contribute to more effective diagnostic and interventional strategies. PMID:21258617

  6. Interaction of metabolic stress with chronic mild stress in altering brain cytokines and sucrose preference.

    PubMed

    Remus, Jennifer L; Stewart, Luke T; Camp, Robert M; Novak, Colleen M; Johnson, John D

    2015-06-01

    There is growing evidence that metabolic stressors increase an organism's risk of depression. Chronic mild stress is a popular animal model of depression and several serendipitous findings have suggested that food deprivation prior to sucrose testing in this model is necessary to observe anhedonic behaviors. Here, we directly tested this hypothesis by exposing animals to chronic mild stress and used an overnight 2-bottle sucrose test (food ad libitum) on Day 5 and 10, then food and water deprive animals overnight and tested their sucrose consumption and preference in a 1-hr sucrose test the following morning. Approximately 65% of stressed animals consumed sucrose and showed a sucrose preference similar to nonstressed controls in an overnight sucrose test, and 35% showed a decrease in sucrose intake and preference. Following overnight food and water deprivation the previously "resilient" animals showed a significant decrease in sucrose preference and greatly reduced sucrose intake. In addition, we evaluated whether the onset of anhedonia following food and water deprivation corresponds to alterations in corticosterone, epinephrine, circulating glucose, or interleukin-1 beta (IL-1β) expression in limbic brain areas. Although all stressed animals showed adrenal hypertrophy and elevated circulating epinephrine, only stressed animals that were food deprived were hypoglycemic compared with food-deprived controls. Additionally, food and water deprivation significantly increased hippocampus IL-1β while food and water deprivation only increased hypothalamus IL-1β in stress-susceptible animals. These data demonstrate that metabolic stress of food and water deprivation interacts with chronic stressor exposure to induce physiological and anhedonic responses. (c) 2015 APA, all rights reserved).

  7. Diagnosis of Posttraumatic Stress Disorder in Preschool Children

    ERIC Educational Resources Information Center

    De Young, Alexandra C.; Kenardy, Justin A.; Cobham, Vanessa E.

    2011-01-01

    This study investigated the existing diagnostic algorithms for posttraumatic stress disorder (PTSD) to determine the most developmentally sensitive and valid approach for diagnosing this disorder in preschoolers. Participants were 130 parents of unintentionally burned children (1-6 years). Diagnostic interviews were conducted with parents to…

  8. Psychotherapeutic and Adjunctive Pharmacologic Approaches to Treating Posttraumatic Stress Disorder

    PubMed Central

    Nisenoff, Carolina D.

    2008-01-01

    Posttraumatic stress disorder (PTSD) is a potentially disabling illness that affects millions of people worldwide and can be very difficult to treat, especially the sleep disturbances often associated with this disorder. Successful treatment focuses on psychotherapy, and medications may be useful adjuncts. This article gives examples of successful therapeutic approaches and adjunctive medication use in PTSD. PMID:19727267

  9. Effects of RSA Feedback on Posttraumatic Stress Disorder Symptomatology

    ERIC Educational Resources Information Center

    Fourie, Phillip

    2006-01-01

    Posttraumatic stress disorder (PTSD) is one of the anxiety disorders with particularly debilitating effects due to flashbacks and hypervigilance in daily life. Treatments commonly focus upon either pharmacological or psychotherapeutic modalities, but there is often a need to merge both of these approaches to deal effectively with the somatic, as…

  10. Neuropsychological Effects of Posttraumatic Stress Disorder in Children and Adolescents

    ERIC Educational Resources Information Center

    Turley, Matthew R.; Obrzut, John E.

    2012-01-01

    Posttraumatic Stress Disorder (PTSD) can affect people of all ages but the literature is lacking on children and adolescents who experience PTSD. The consequences of this disorder extend beyond the basic symptoms by which it is defined. Neuroanatomically, the brains of children with PTSD have been found to be abnormally symmetrical in several…

  11. The Relationship between Sexual Abuse and Post Traumatic Stress Disorder.

    ERIC Educational Resources Information Center

    Lawson, David Allen

    Post Traumatic Stress Disorder (PTSD) is a fairly recent inclusion in the literature as a psychiatric disorder. Currently, researchers are trying to relate PTSD to many different environmental and psychosocial stressors including physical abuse, emotional abuse, war trauma, and sexual abuse. This paper addresses research concerning the…

  12. Diagnosis of Posttraumatic Stress Disorder in Preschool Children

    ERIC Educational Resources Information Center

    De Young, Alexandra C.; Kenardy, Justin A.; Cobham, Vanessa E.

    2011-01-01

    This study investigated the existing diagnostic algorithms for posttraumatic stress disorder (PTSD) to determine the most developmentally sensitive and valid approach for diagnosing this disorder in preschoolers. Participants were 130 parents of unintentionally burned children (1-6 years). Diagnostic interviews were conducted with parents to…

  13. Neuropsychological Effects of Posttraumatic Stress Disorder in Children and Adolescents

    ERIC Educational Resources Information Center

    Turley, Matthew R.; Obrzut, John E.

    2012-01-01

    Posttraumatic Stress Disorder (PTSD) can affect people of all ages but the literature is lacking on children and adolescents who experience PTSD. The consequences of this disorder extend beyond the basic symptoms by which it is defined. Neuroanatomically, the brains of children with PTSD have been found to be abnormally symmetrical in several…

  14. Behavioral Interventions for Trauma and Posttraumatic Stress Disorder

    ERIC Educational Resources Information Center

    Hassija, Christina M.; Gray, Matt J.

    2007-01-01

    Optimal therapy for Posttraumatic Stress Disorder (PTSD) follows logically from an understanding of etiological models describing the development and maintenance of the disorder. Accordingly, the present article provides a brief overview of PTSD with particular attention paid to etiology. Exposure-based interventions have consistently been shown…

  15. Effects of RSA Feedback on Posttraumatic Stress Disorder Symptomatology

    ERIC Educational Resources Information Center

    Fourie, Phillip

    2006-01-01

    Posttraumatic stress disorder (PTSD) is one of the anxiety disorders with particularly debilitating effects due to flashbacks and hypervigilance in daily life. Treatments commonly focus upon either pharmacological or psychotherapeutic modalities, but there is often a need to merge both of these approaches to deal effectively with the somatic, as…

  16. [Clinical approach to post-traumatic stress disorders].

    PubMed

    Boussaud, Marie

    2015-01-01

    A confrontation with death can lead to acute reactions of stress, followed possibly, after a phase of latency, by post-traumatic stress disorder (PTSD). PTSD is characterised by the appearance of a repetition syndrome combining reliving, hypervigilance and avoidance; comorbidities frequently arise, increasingthe risk of suicide. Caregivers have an important role to play in identifying them.

  17. Production of Syllable Stress in Speakers with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Paul, Rhea; Bianchi, Nancy; Augustyn, Amy; Klin, Ami; Volkmar, Fred R.

    2008-01-01

    This paper reports a study of the ability to reproduce stress in a nonsense syllable imitation task by adolescent speakers with autism spectrum disorders (ASD), as compared to typically developing (TD) age-mates. Results are reported for both raters' judgments of the subjects' stress production, as well as acoustic measures of pitch range and…

  18. The Neurocircuitry of Fear, Stress, and Anxiety Disorders

    PubMed Central

    Shin, Lisa M; Liberzon, Israel

    2010-01-01

    Anxiety disorders are a significant problem in the community, and recent neuroimaging research has focused on determining the brain circuits that underlie them. Research on the neurocircuitry of anxiety disorders has its roots in the study of fear circuits in animal models and the study of brain responses to emotional stimuli in healthy humans. We review this research, as well as neuroimaging studies of anxiety disorders. In general, these studies have reported relatively heightened amygdala activation in response to disorder-relevant stimuli in post-traumatic stress disorder, social phobia, and specific phobia. Activation in the insular cortex appears to be heightened in many of the anxiety disorders. Unlike other anxiety disorders, post-traumatic stress disorder is associated with diminished responsivity in the rostral anterior cingulate cortex and adjacent ventral medial prefrontal cortex. Additional research will be needed to (1) clarify the exact role of each component of the fear circuitry in the anxiety disorders, (2) determine whether functional abnormalities identified in the anxiety disorders represent acquired signs of the disorders or vulnerability factors that increase the risk of developing them, (3) link the findings of functional neuroimaging studies with those of neurochemistry studies, and (4) use functional neuroimaging to predict treatment response and assess treatment-related changes in brain function. PMID:19625997

  19. Neural circuits in anxiety and stress disorders: a focused review

    PubMed Central

    Duval, Elizabeth R; Javanbakht, Arash; Liberzon, Israel

    2015-01-01

    Anxiety and stress disorders are among the most prevalent neuropsychiatric disorders. In recent years, multiple studies have examined brain regions and networks involved in anxiety symptomatology in an effort to better understand the mechanisms involved and to develop more effective treatments. However, much remains unknown regarding the specific abnormalities and interactions between networks of regions underlying anxiety disorder presentations. We examined recent neuroimaging literature that aims to identify neural mechanisms underlying anxiety, searching for patterns of neural dysfunction that might be specific to different anxiety disorder categories. Across different anxiety and stress disorders, patterns of hyperactivation in emotion-generating regions and hypoactivation in prefrontal/regulatory regions are common in the literature. Interestingly, evidence of differential patterns is also emerging, such that within a spectrum of disorders ranging from more fear-based to more anxiety-based, greater involvement of emotion-generating regions is reported in panic disorder and specific phobia, and greater involvement of prefrontal regions is reported in generalized anxiety disorder and posttraumatic stress disorder. We summarize the pertinent literature and suggest areas for continued investigation. PMID:25670901

  20. Conduct disorder, war zone stress, and war-related posttraumatic stress disorder symptoms in American Indian Vietnam veterans.

    PubMed

    Dillard, Denise; Jacobsen, Clemma; Ramsey, Scott; Manson, Spero

    2007-02-01

    This study examined whether conduct disorder (CD) was associated with war zone stress and war-related post-traumatic stress disorder (PTSD) symptoms in American Indian (AI) Vietnam veterans. Cross-sectional lay-interview data was analyzed for 591 male participants from the American Indian Vietnam Veterans Project. Logistic regression evaluated the association of CD with odds of high war zone stress and linear regression evaluated the association of CD and PTSD symptom severity. Childhood CD was not associated with increased odds of high war zone stress. Conduct disorder was associated with elevated war-related PTSD symptoms among male AI Vietnam Veterans independent of war zone stress level and other mediators. Future efforts should examine reasons for this association and if the association exists in other AI populations.

  1. Activation of ATP-sensitive potassium channel by iptakalim normalizes stress-induced HPA axis disorder and depressive behaviour by alleviating inflammation and oxidative stress in mouse hypothalamus.

    PubMed

    Zhao, Xiao-Jie; Zhao, Zhan; Yang, Dan-Dan; Cao, Lu-Lu; Zhang, Ling; Ji, Juan; Gu, Jun; Huang, Ji-Ye; Sun, Xiu-Lan

    2017-02-01

    Stress-induced disturbance of the hypothalamic-pituitary-adrenal (HPA) axis is strongly implicated in incidence of mood disorders. A heightened neuroinflammatory response and oxidative stress play a fundamental role in the dysfunction of the HPA axis. We have previously demonstrated that iptakalim (Ipt), a new ATP-sensitive potassium (K-ATP) channel opener, could prevent oxidative injury and neuroinflammation against multiple stimuli-induced brain injury. The present study was to demonstrate the impacts of Ipt in stress-induced HPA axis disorder and depressive behavior. We employed 2 stress paradigms: 8 weeks of continuous restraint stress (chronic restraint stress, CRS) and 2h of restraint stress (acute restraint stress, ARS), to mimic both chronic stress and severe acute stress. Prolonged (4 weeks) and short-term (a single injection) Ipt treatment was administered 30min before each stress paradigm. We found that HPA axis was altered after stress, with different responses to CRS (lower ACTH and CORT, higher AVP, but normal CRH) and ARS (higher CRH, ACTH and CORT, but normal AVP). Both prolonged and short-term Ipt treatment normalized stress-induced HPA axis disorders and abnormal behaviors in mice. CRS and ARS up-regulated mRNA levels of inflammation-related molecules (TNFα, IL-1β, IL-6 and TLR4) and oxidative stress molecules (gp91phox, iNOS and Nrf2) in the mouse hypothalamus. Double immunofluorescence showed CRS and ARS increased microglia activation (CD11b and TNFα) and oxidative stress in neurons (NeuN and gp91phox), which were alleviated by Ipt. Therefore, the present study reveals that Ipt could prevent against stress-induced HPA axis disorders and depressive behavior by alleviating inflammation and oxidative stress in the hypothalamus.

  2. The Root Cause of Post-traumatic and Developmental Stress Disorder

    DTIC Science & Technology

    2010-05-01

    work seeks to extend these findings to PTSD. Project 2 ( Fluoxetine in active duty troops) has begun to enroll subjects at Fort Hood and will provide...we have begun patient recruitment on a therapeutic trial of the serotonin reuptake inhibitor fluoxetine , to determine whether it can alter the...investigate genetic factors influencing resiliency and susceptibility to stress disorders and therapeutic response to fluoxetine . Projects 4 and 5 are

  3. [Diagnostic and clinical aspects of complex post-traumatic stress disorder].

    PubMed

    Sack, M

    2004-05-01

    The symptomatology of patients suffering in the aftermath of severe and prolonged traumatization is not entirely covered by the diagnostic criteria of post-traumatic stress disorder (PTSD). Consequently, the concept of complex PTSD was proposed, including symptoms of affective dysregulation, dissociation and somatization, alterations in self-perception, altered relationships with others, and altered systems of meaning. Thereby, a variety of symptoms usually classified as co-morbid disorders are combined in a single etiological model. The whole symptomatology is considered as more or less effective adaptation strategies and not primarily as deficits. This understand-ing of the underlying etiology in subjects with complex traumatization opens perspectives for new psychotherapeutic treatment strategies which have already shown effectiveness in daily practice.

  4. Hippocampus and amygdala volumes in patients with borderline personality disorder with or without posttraumatic stress disorder

    PubMed Central

    Schmahl, Christian; Berne, Kevin; Krause, Annegret; Kleindienst, Nikolaus; Valerius, Gabriele; Vermetten, Eric; Bohus, Martin

    2009-01-01

    Background Several studies have investigated volumetric brain changes in patients with posttraumatic stress disorder (PTSD) and borderline personality disorder (BPD). Both groups exhibit volume reductions of the hippocampus and amygdala. Our aim was to investigate the influence of comorbid PTSD on hippocampus and amygdala volumes in patients with BPD. Methods We compared 2 groups of unmedicated female patients with BPD (10 with and 15 without comorbid PTSD) and 25 healthy female controls. We used T1- and T2-weighted magnetic resonance images for manual tracing and 3-dimensional reconstruction of the hippocampus and amygdala. Results Hippocampus volumes of patients with BPD and PTSD were smaller than those of healthy controls. However, there was no significant difference between patients with BPD but without PTSD and controls. Impulsiveness was positively correlated with hippocampus volumes in patients with BPD. Limitations Our study did not allow for disentangling the effects of PTSD and traumatization. Another limitation was the relatively small sample size. Conclusion Our findings highlight the importance of classifying subgroups of patients with BPD. Comorbid PTSD may be related to volumetric alterations in brain regions that are of central importance to our understanding of borderline psychopathology. PMID:19568480

  5. Peritraumatic versus persistent dissociation in acute stress disorder.

    PubMed

    Panasetis, Paula; Bryant, Richard A

    2003-12-01

    The DSM-IV definition of acute stress disorder (ASD) regards dissociation that occurs during a trauma (peritraumatic dissociation) comparably to persistent dissociation. This study investigated the relative contributions of peritraumatic dissociation and persistent dissociation to acute posttraumatic stress reactions. Civilian trauma (N = 53) survivors with either acute stress disorder (ASD), subclinical ASD, or no ASD were administered modified versions of the Peritraumatic Dissociative Experiences Questionnaire that indexed both dissociation during the trauma and dissociation at the time of assessment. Persistent dissociation was more strongly associated with ASD severity and intrusive symptoms than peritraumatic dissociation. These results are consistent with the proposition that persistent, rather than peritraumatic, dissociation is associated with posttraumatic psychopathology.

  6. Prenatal stress and inhibitory neuron systems: implications for neuropsychiatric disorders

    PubMed Central

    Fine, Rebecca; Zhang, Jie; Stevens, Hanna E.

    2014-01-01

    Prenatal stress is a risk factor for several psychiatric disorders in which inhibitory neuron pathology is implicated. A growing body of research demonstrates that inhibitory circuitry in the brain is directly and persistently affected by prenatal stress. This review synthesizes research that elucidates how this early, developmental risk factor impacts inhibitory neurons and how these findings intersect with research on risk factors and inhibitory neuron pathophysiology in schizophrenia, anxiety, autism and Tourette syndrome. The specific impact of prenatal stress on inhibitory neurons, particularly developmental mechanisms, may elucidate further the pathophysiology of these disorders. PMID:24751963

  7. Tryptophan Hydroxylase-2: An Emerging Therapeutic Target for Stress Disorders

    PubMed Central

    Chen, Guo-Lin; Miller, Gregory M.

    2013-01-01

    Serotonin (5-HT) has been long recognized to modulate the stress response, and dysfunction of 5-HT has been implicated in numerous stress disorders. Accordingly, the 5-HT system has been targeted for the treatment of stress disorders. Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in 5-HT synthesis, and the recent identification of a second, neuron-specific TPH isoform (TPH2) opened up a new area of research. With a decade of extensive investigation, it is now recognized that: 1) TPH2 exhibits a highly flexible gene expression that is modulated by an increasing number of internal and external environmental factors including the biological clock, stressors, endogenous hormones, and antidepressant therapies; and 2) genetically determined TPH2 activity is linked to a growing body of stress-related neuronal correlates and behavioral traits. These findings reveal an active role of TPH2 in the stress response and provide new insights into the long recognized but not yet fully understood 5-HT-stress interaction. As a major modulator of 5-HT neurotransmission and the stress response, TPH2 is of both pathophysiological and pharmacological significance, and is emerging as a new therapeutic target for the treatment of stress disorders. Given that numerous antidepressant therapies influence TPH2 gene expression, TPH2 is already inadvertently targeted for the treatment of stress disorders. With increased understanding of the regulation of TPH2 activity we can now purposely utilize TPH2 as a target to develop new or optimize current therapies, which are expected to greatly improve the prevention and treatment of a wide variety of stress disorders. PMID:23435356

  8. Post-Traumatic Stress Disorder (PTSD)

    MedlinePlus

    ... NIH Record For the Press Radio Podcast Videocast Multimedia News in Health Newsletter Research Matters Weekly Research ... in which a training procedure can alter it. Learning not to fear, a process called fear extinction, ...

  9. Adjustment disorders as a stress-related disorder: a longitudinal study of the associations among stress, resources, and mental health.

    PubMed

    Kocalevent, Rüya-Daniela; Mierke, Annett; Danzer, Gerhard; Klapp, Burghard F

    2014-01-01

    Adjustment disorders are re-conceptualized in the DSM-5 as a stress-related disorder; however, besides the impact of an identifiable stressor, the specification of a stress concept, remains unclear. This study is the first to examine an existing stress-model from the general population, in patients diagnosed with adjustment disorders, using a longitudinal design. The study sample consisted of 108 patients consecutively admitted for adjustment disorders. Associations of stress perception, emotional distress, resources, and mental health were measured at three time points: the outpatients' presentation, admission for inpatient treatment, and discharge from the hospital. To evaluate a longitudinal stress model of ADs, we examined whether stress at admission predicted mental health at each of the three time points using multiple linear regressions and structural equation modeling. A series of repeated-measures one-way analyses of variance (rANOVAs) was performed to assess change over time. Significant within-participant changes from baseline were observed between hospital admission and discharge with regard to mental health, stress perception, and emotional distress (p<0.001). Stress perception explained nearly half of the total variance (44%) of mental health at baseline; the adjusted R2 increased (0.48), taking emotional distress (i.e., depressive symptoms) into account. The best predictor of mental health at discharge was the level of emotional distress (i.e., anxiety level) at baseline (β= -0.23, R2corr=0.56, p<0.001). With a CFI of 0.86 and an NFI of 0.86, the fit indices did not allow for acceptance of the stress-model (Cmin/df=15.26; RMSEA=0.21). Stress perception is an important predictor in adjustment disorders, and mental health-related treatment goals are dependent on and significantly impacted by stress perception and emotional distress.

  10. Adjustment Disorders as a Stress-Related Disorder: A Longitudinal Study of the Associations among Stress, Resources, and Mental Health

    PubMed Central

    Kocalevent, Rüya-Daniela; Mierke, Annett; Danzer, Gerhard; Klapp, Burghard F.

    2014-01-01

    Objective Adjustment disorders are re-conceptualized in the DSM-5 as a stress-related disorder; however, besides the impact of an identifiable stressor, the specification of a stress concept, remains unclear. This study is the first to examine an existing stress-model from the general population, in patients diagnosed with adjustment disorders, using a longitudinal design. Methods The study sample consisted of 108 patients consecutively admitted for adjustment disorders. Associations of stress perception, emotional distress, resources, and mental health were measured at three time points: the outpatients’ presentation, admission for inpatient treatment, and discharge from the hospital. To evaluate a longitudinal stress model of ADs, we examined whether stress at admission predicted mental health at each of the three time points using multiple linear regressions and structural equation modeling. A series of repeated-measures one-way analyses of variance (rANOVAs) was performed to assess change over time. Results Significant within-participant changes from baseline were observed between hospital admission and discharge with regard to mental health, stress perception, and emotional distress (p<0.001). Stress perception explained nearly half of the total variance (44%) of mental health at baseline; the adjusted R2 increased (0.48), taking emotional distress (i.e., depressive symptoms) into account. The best predictor of mental health at discharge was the level of emotional distress (i.e., anxiety level) at baseline (β = −0.23, R2corr = 0.56, p<0.001). With a CFI of 0.86 and an NFI of 0.86, the fit indices did not allow for acceptance of the stress-model (Cmin/df = 15.26; RMSEA = 0.21). Conclusions Stress perception is an important predictor in adjustment disorders, and mental health-related treatment goals are dependent on and significantly impacted by stress perception and emotional distress. PMID:24825165

  11. Differential alterations of resting-state functional connectivity in generalized anxiety disorder and panic disorder.

    PubMed

    Cui, Huiru; Zhang, Jie; Liu, Yicen; Li, Qingwei; Li, Hui; Zhang, Lanlan; Hu, Qiang; Cheng, Wei; Luo, Qiang; Li, Jianqi; Li, Wei; Wang, Jijun; Feng, Jianfeng; Li, Chunbo; Northoff, Georg

    2016-04-01

    Generalized anxiety disorder (GAD) and panic disorder (PD) are most common anxiety disorders with high lifetime prevalence while the pathophysiology and disease-specific alterations still remain largely unclear. Few studies have taken a whole-brain perspective in the functional connectivity (FC) analysis of these two disorders in resting state. It limits the ability to identify regionally and psychopathologically specific network abnormalities with their subsequent use as diagnostic marker and novel treatment strategy. The whole brain FC using a novel FC metric was compared, that is, scaled correlation, which they demonstrated to be a reliable FC statistics, but have higher statistical power in two-sample t-test of whole brain FC analysis. About 21 GAD and 18 PD patients were compared with 22 matched control subjects during resting-state, respectively. It was found that GAD patients demonstrated increased FC between hippocampus/parahippocampus and fusiform gyrus among the most significantly changed FC, while PD was mainly associated with greater FC between somatosensory cortex and thalamus. Besides such regional specificity, it was observed that psychopathological specificity in that the disrupted FC pattern in PD and GAD correlated with their respective symptom severity. The findings suggested that the increased FC between hippocampus/parahippocampus and fusiform gyrus in GAD were mainly associated with a fear generalization related neural circuit, while the greater FC between somatosensory cortex and thalamus in PD were more likely linked to interoceptive processing. Due to the observed regional and psychopathological specificity, their findings bear important clinical implications for the potential treatment strategy. © 2016 Wiley Periodicals, Inc.

  12. Role of NAD+, Oxidative Stress, and Tryptophan Metabolism in Autism Spectrum Disorders

    PubMed Central

    Essa, Musthafa Mohamed; Subash, Selvaraju; Braidy, Nady; Al-Adawi, Samir; Lim, Chai K; Manivasagam, Tamilarasan; Guillemin, Gilles J

    2013-01-01

    Autism spectrum disorder (ASD) is a pervasive neuro-developmental disorder characterized by impaired social interaction, reduced/absent verbal and non-verbal communication, and repetitive behavior during early childhood. The etiology of this developmental disorder is poorly understood, and no biomarkers have been identified. Identification of novel biochemical markers related to autism would be advantageous for earlier clinical diagnosis and intervention. Studies suggest that oxidative stress-induced mechanisms and reduced antioxidant defense, mitochondrial dysfunction, and impaired energy metabolism (NAD+, NADH, ATP, pyruvate, and lactate), are major causes of ASD. This review provides renewed insight regarding current autism research related to oxidative stress, mitochondrial dysfunction, and altered tryptophan metabolism in ASD. PMID:23922500

  13. Relations between anger and DSM-5 posttraumatic stress disorder symptoms.

    PubMed

    Durham, Tory A; Byllesby, Brianna M; Armour, Cherie; Forbes, David; Elhai, Jon D

    2016-10-30

    The present study investigated the relationship between posttraumatic stress disorder (PTSD) and anger. Anger co-occurring with PTSD is found to have a severe effect across a wide range of traumatic experiences, making this an important relationship to examine. The present study utilized data regarding dimensions of PTSD symptoms and anger collected from a non-clinical sample of 247 trauma-exposed participants. Confirmatory factor analysis (CFA) was used to determine the underlying factor structure of both PTSD and anger by examining anger in the context of three models of PTSD. Results indicate that a five-factor representation of PTSD and one-factor representation of anger fit the data best. Additionally, anger demonstrated a strong relationship with the dysphoric arousal and negative alterations in cognitions and mood (NACM) factors; and dysphoric arousal was differentially related to anger. Clinical implications include potential need to reevaluate PTSD's diagnostic symptom structure and highlight the potential need to target and treat comorbid anger in individuals with PTSD. In regard to research, these results support the heterogeneity of PTSD.

  14. Glucocorticoid Receptor and FKBP5 Expression Is Altered Following Exposure to Chronic Stress: Modulation by Antidepressant Treatment

    PubMed Central

    Guidotti, Gianluigi; Calabrese, Francesca; Anacker, Christoph; Racagni, Giorgio; Pariante, Carmine M; Riva, Marco A

    2013-01-01

    Major depression is thought to originate from the interaction between susceptibility genes and adverse environmental events, in particular stress. The hypothalamus–pituitary–adrenal (HPA) axis is the major system involved in stress response and its dysregulation is an important element in the pathogenesis of depression. The stress response is therefore finely tuned through a series of mechanisms that control the trafficking of glucocorticoid receptors (GRs) to the nucleus, including binding to the chaperone protein FKBP5 and receptor phosphorylation, suggesting that these elements may also be affected under pathologic conditions. On these bases, we investigated FKBP5 and GR expression and phosphorylation in the hippocampus (ventral and dorsal) and in the prefrontal cortex of rats exposed to chronic mild stress (CMS) and we analyzed the effect of a concomitant antidepressant treatment. We found that animals exposed to CMS show increased expression of FKBP5 as well as enhanced cytoplasmic levels of GR, primarily in ventral hippocampus and prefrontal cortex. Chronic treatment with the antidepressant duloxetine is able to normalize such alterations, mainly in the prefrontal cortex. Moreover, we demonstrate that CMS-induced alterations of GR trafficking and transcription may be sustained by changes in receptor phosphorylation, which are also modulated by pharmacological intervention. In summary, while GR-related changes after CMS might be relevant for the depressive phenotype, the ability of antidepressant treatment to correct some of these alterations may contribute to the normalization of HPA axis dysfunctions associated with stress-related disorders. PMID:23169346

  15. Neuroinflammatory pathways in anxiety, posttraumatic stress, and obsessive compulsive disorders.

    PubMed

    Furtado, Melissa; Katzman, Martin A

    2015-09-30

    As prevalence of anxiety, posttraumatic stress, and obsessive compulsive disorders continue to rise worldwide, increasing focus has been placed on immune mediated theories in understanding the underlying mechanisms of these disorders. Associations between the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and these disorders have been recognized in the scientific literature, specifically in regard to cortisol levels, as well as changes in pro- and anti-inflammatory cytokines. The present commentary will systematically assess the scientific literature within the past decade in regard to the psychoneuroimmunology of anxiety, posttraumatic stress, and obsessive compulsive disorders. Understanding the mechanisms of these disorders is essential in order to determine efficacious and targeted treatment strategies, which may lead to substantial improvements in overall functioning, as well as significant decreases in societal and economic burden.

  16. Longitudinal Associations between Posttraumatic Stress Disorder Severity and Personality Disorder Features among Female Rape Survivors

    PubMed Central

    Bovin, Michelle J.; Wolf, Erika J.; Resick, Patricia A.

    2017-01-01

    This study evaluated how change in posttraumatic stress disorder (PTSD) symptoms was associated with residualized change in comorbid personality disorder (PD) features and vice versa over the course of 5–10 years. The sample was comprised of 79 female rape survivors who met criteria for PTSD and who were a part of a larger study examining the effects of trauma-focused therapy. PTSD was assessed with the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) version of the Clinician-Administered PTSD Scale [CAPS-IV (1)] and PD features were assessed with the DSM-IV dimensional PD scales on the Schedule for Non-adaptive and Adaptive Personality [SNAP (2)]. PTSD symptom severity and PD features were assessed at baseline and between 5 and 10 years after completing treatment. Multiple regression analyses revealed that PTSD symptom change was related to residualized change in PD severity for paranoid, schizotypal, antisocial, borderline, avoidant, and dependent PD (βs ranged from −0.23 to −0.33; all ps < 0.05). In addition, for borderline and antisocial PDs, longitudinal stability of the PD was attenuated among those with greater PTSD symptom improvement (i.e., the relationship between these PDs over time was altered as a function of PTSD symptom change; βs ranged from −0.27 to −0.29; all ps < 0.05). Similarly, change in severity of paranoid, schizotypal, antisocial, avoidant, and obsessive–compulsive (OC) PD was associated with residualized change in PTSD symptoms (βs ranged from −0.32 to −0.41; all ps < 0.05), and the longitudinal stability of PTSD was attenuated as a product of change in OC PD (β = −0.27; p < 0.02). These findings suggest that these two sets of disorders may impact one another substantially, altering the course of even chronic, characterological conditions. This carries important clinical implications for the treatment of both PTSD and PDs. PMID:28210229

  17. Alterations in magnesium and oxidative status during chronic emotional stress.

    PubMed

    Cernak, I; Savic, V; Kotur, J; Prokic, V; Kuljic, B; Grbovic, D; Veljovic, M

    2000-03-01

    Magnesium and oxidative status were investigated in young volunteers exposed to chronic stress (political intolerance, awareness of potential military attacks, permanent stand-by duty and reduced holidays more than 10 years) or subchronic stress consisting of everyday mortal danger in military actions lasting more than 3 months. Significant decreases in plasma ionized Mg2+, total Mg and ionized Ca2+ concentrations were found in both groups. Similarly, both study groups exhibited oxidative stress as assessed by increased plasma superoxide anions and malondialdehyde and modified antioxidant defense. There were no significant differences between the two stress groups. A negative correlation between magnesium balance and oxidative stress was observed suggesting that the same etiological factor (chronic stress) initiate decreases in both free and total magnesium concentrations and simultaneously increase oxidative stress intensity. These findings support the need for magnesium supplementation with antioxidant vitamins for people living in conditions of chronic stress.

  18. Posttraumatic stress disorder in survivors of the Brooklyn Bridge shooting.

    PubMed

    Trappler, B; Friedman, S

    1996-05-01

    The authors documented the frequency of posttraumatic stress disorder (PTSD) in civilian victims of urban terrorism. A recent shooting attack on a van of Hasidic students provided a unique opportunity to document responses of survivors in this targeted group. Eleven of 14 survivors were compared with age-matched subjects on a variety of questionnaires and clinical evaluations. Of the 11 survivors, four were diagnosed with PTSD (all of whom also had concurrent major depressive disorder), one with major depressive disorder, and two with adjustment disorder. Findings are interpreted in the context of unique factors contributing to the heightened vulnerability of this group.

  19. Sleep and Posttraumatic Stress Disorder (PTSD)

    MedlinePlus

    ... the bottom of the page. Share this page Search PTSD Site Choose Section Enter Term and Search ... Coach Online Tools to help you manage stress. Search Pilots Search PILOTS *, the largest citation database on ...

  20. Post-Traumatic Stress Disorder (PDQ)

    MedlinePlus

    ... traumatic stress may be triggered when certain smells, sounds, and sights are linked with chemotherapy or other treatments. Post- ... an upsetting event. Neutral triggers (such as smells, sounds, and sights) that occurred at the same time as upsetting ...

  1. Sex, stress, and epigenetics: regulation of behavior in animal models of mood disorders

    PubMed Central

    2013-01-01

    Women have a higher incidence of stress related disorders including depression and generalized anxiety disorder, and epigenetic mechanisms likely contribute to this sex difference. Evidence from preclinical research suggests that epigenetic mechanisms are responsible for both sexual dimorphism of brain regions and sensitivity of the stress response. Epigenetic modifications such as DNA methylation and histone modifications can occur transgenerationally, developmentally, or in response to environmental stimuli such as stress exposure. This review will provide an overview of the various forms of epigenetic modifications observed in the central nervous system and will explain how these mechanisms contribute to a sexually dimorphic brain. It will also discuss the ways in which epigenetic alterations coincide with, and functionally contribute to, the behavioral response to stress across the lifespan. Ultimately, this review will focus on novel research utilizing animal models to investigate sex differences in epigenetic mechanisms that influence susceptibility to stress. Exploration of this relationship reveals epigenetic mechanisms with the potential to explain sexual dimorphism in the occurrence of stress related disorders. PMID:23331332

  2. Cerebrovascular expression of proteins related to inflammation, oxidative stress and neurotoxicity is altered with aging

    PubMed Central

    2010-01-01

    Background Most neurodegenerative diseases are age-related disorders; however, how aging predisposes the brain to disease has not been adequately addressed. The objective of this study is to determine whether expression of proteins in the cerebromicrovasculature related to inflammation, oxidative stress and neurotoxicity is altered with aging. Methods Brain microvessels are isolated from Fischer 344 rats at 6, 12, 18 and 24 months of age. Levels of interleukin (IL)-1β and IL-6 RNA are determined by RT-PCR and release of cytokines into the media by ELISA. Vessel conditioned media are also screened by ELISA for IL-1α, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α, (TNFα), and interferon γ (IFNγ). Immunofluorescent analysis of brain sections for IL-1β and IL-6 is performed. Results Expression of IL-1β and IL-6, both at RNA and protein levels, significantly (p < 0.01) decreases with age. Levels of MCP-1, TNFα, IL-1α, and IFNγ are significantly (p < 0.05-0.01) lower in 24 month old rats compared to 6 month old animals. Immunofluorescent analysis of brain vessels also shows a decline in IL-1β and IL-6 in aged rats. An increase in oxidative stress, assessed by increased carbonyl formation, as well as a decrease in the antioxidant protein manganese superoxide dismutase (MnSOD) is evident in vessels of aged animals. Finally, addition of microvessel conditioned media from aged rats to neuronal cultures evokes significant (p < 0.001) neurotoxicity. Conclusions These data demonstrate that cerebrovascular expression of proteins related to inflammation, oxidative stress and neurotoxicity is altered with aging and suggest that the microvasculature may contribute to functional changes in the aging brain. PMID:20937133

  3. Trigeminal Nerve Stimulation for Comorbid Posttraumatic Stress Disorder and Major Depressive Disorder.

    PubMed

    Cook, Ian A; Abrams, Michelle; Leuchter, Andrew F

    2016-04-01

    External stimulation of the trigeminal nerve (eTNS) is an emerging neuromodulation therapy for epilepsy and depression. Preliminary studies suggest it has an excellent safety profile and is associated with significant improvements in seizures and mood. Neuroanatomical projections of the trigeminal system suggest eTNS may alter activity in structures regulating mood, anxiety, and sleep. In this proof-of-concept trial, the effects of eTNS were evaluated in adults with posttraumatic stress disorder (PTSD) and comorbid unipolar major depressive disorder (MDD) as an adjunct to pharmacotherapy for these commonly co-occurring conditions. Twelve adults with PTSD and MDD were studied in an eight-week open outpatient trial (age 52.8 [13.7 sd], 8F:4M). Stimulation was applied to the supraorbital and supratrochlear nerves for eight hours each night as an adjunct to pharmacotherapy. Changes in symptoms were monitored using the PTSD Patient Checklist (PCL), Hamilton Depression Rating Scale (HDRS-17), Quick Inventory of Depressive Symptomatology (QIDS-C), and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). Over the eight weeks, eTNS treatment was associated with significant decreases in PCL (p = 0.003; median decrease of 15 points; effect size d 1.5), HDRS-17 (p < 0.001; 42% response rate, 25% remission; d 2.1), and QIDS-C scores (p < 0.001; d 1.8), as well as an improvement in quality of life (Q-LES-Q, p < 0.01). eTNS was well tolerated with few treatment emergent adverse events. Significant improvements in PTSD and depression severity were achieved in the eight weeks of acute eTNS treatment. This novel approach to wearable brain stimulation may have use as an adjunct to pharmacotherapy in these disorders if efficacy and tolerability are confirmed with additional studies. © 2016 International Neuromodulation Society.

  4. Analyses of antioxidant status and nucleotide alterations in genes encoding antioxidant enzymes in patients with benign and malignant thyroid disorders.

    PubMed

    Ramli, Nur Siti Fatimah; Mat Junit, Sarni; Leong, Ng Khoon; Razali, Nurhanani; Jayapalan, Jaime Jacqueline; Abdul Aziz, Azlina

    2017-01-01

    Synthesis of thyroid hormones and regulation of their metabolism involve free radicals that may affect redox balance in the body. Thyroid disorders causing variations in the levels of thyroid hormones may alter cellular oxidative stress. The aim of this study was to measure the antioxidant activities and biomarkers of oxidative stress in serum and red blood cells (RBC) of patients with benign and malignant thyroid disorders and to investigate if changes in the antioxidant activities in these patients were linked to alterations in genes encoding the antioxidant enzymes. Forty-one patients with thyroid disorders from University of Malaya Medical Centre were recruited. They were categorised into four groups: multinodular goitre (MNG) (n = 18), follicular thyroid adenoma (FTA) (n = 7), papillary thyroid cancer (PTC) (n = 10), and follicular thyroid cancer (FTC) (n = 6). Serum and RBC of patients were analysed for antioxidant activities, antioxidant enzymes, and biomarkers of oxidative stress. Alterations in genes encoding the antioxidant enzymes were analysed using whole exome sequencing and PCR-DNA sequencing. Patients with thyroid disorders had significantly higher serum superoxide dismutase (SOD) and catalase (CAT) activities compared to control, but had lower activities in RBC. There were no significant changes in serum glutathione peroxidase (GPx) activity. Meanwhile, GPx activity in RBC was reduced in PTC and FTC, compared to control and the respective benign groups. Antioxidant activities in serum were decreased in the thyroid disorder groups when compared to the control group. The levels of malondialdehyde (MDA) were elevated in the serum of FTA group when compared to controls, while in the RBC, only the MNG and PTC groups showed higher MDA equivalents than control. Serum reactive oxygen species (ROS) levels in PTC group of both serum and RBC were significantly higher than control group. Whole exome sequencing has resulted in identification of 49 single

  5. Preclinical perspectives on posttraumatic stress disorder criteria in DSM-5.

    PubMed

    Tye, Susannah; Van Voorhees, Elizabeth; Hu, Chunling; Lineberry, Timothy

    2015-01-01

    Posttraumatic stress disorder (PTSD) now sits within the newly created "Trauma- and Stressor-Related Disorders" section of the Diagnostic and Statistical Manual of Mental Disorders (fifth edition; DSM-5). Through the refinement and expansion of diagnostic criteria, the DSM-5 version better clarifies the broad and pervasive effects of trauma on functioning, as well as the impact of development on trauma reactions. Aggressive and dissociative symptoms are more thoroughly characterized, reflecting increasing evidence that reactions to trauma often reach beyond the domains of fear and anxiety (these latter domains were emphasized in DSM-IV). These revised criteria are supported by decades of preclinical and clinical research quantifying traumatic stress-induced changes in neurobiological and behavioral function. Several features of the DSM-5 PTSD criteria are similarly and consistently represented in preclinical animal models and humans following exposure to extreme stress. In rodent models, for example, increases in anxiety-like, helplessness, or aggressive behavior, along with disruptions in circadian/neurovegetative function, are typically induced by severe, inescapable, and uncontrollable stress. These abnormalities are prominent features of PTSD and can help us in understanding the pathophysiology of this and other stress-associated psychiatric disorders. In this article we examine some of the changes to the diagnostic criteria of PTSD in the context of trauma-related neurobiological dysfunction, and discuss implications for how preclinical data can be useful in current and future clinical conceptualizations of trauma and trauma-related psychiatric disorders.

  6. Post-traumatic stress disorder and cardiovascular disease.

    PubMed

    Edmondson, Donald; von Känel, Roland

    2017-04-01

    In this paper, a first in a Series of two, we look at the evidence for an association of post-traumatic stress disorder with incident cardiovascular disease risk and the mechanisms that might cause this association, as well as the prevalence of post-traumatic stress disorder due to cardiovascular disease events and its associated prognostic risk. We discuss research done after the publication of previous relevant systematic reviews, and survey currently funded research from the two most active funders in the field: the National Institutes of Health and the US Veterans Administration. We conclude that post-traumatic stress disorder is a risk factor for incident cardiovascular disease, and a common psychiatric consequence of cardiovascular disease events that might worsen the prognosis of the cardiovascular disease. There are many candidate mechanisms for the link between post-traumatic stress disorder and cardiovascular disease, and several ongoing studies could soon point to the most important behavioural and physiological mechanisms to target in early phase intervention development. Similarly, targets are emerging for individual and environmental interventions that might offset the risk of post-traumatic stress disorder after cardiovascular disease events.

  7. Genetic approaches to understanding post-traumatic stress disorder.

    PubMed

    Almli, Lynn M; Fani, Negar; Smith, Alicia K; Ressler, Kerry J

    2014-02-01

    Post-traumatic stress disorder (PTSD) is increasingly recognized as both a disorder of enormous mental health and societal burden, but also as an anxiety disorder that may be particularly understandable from a scientific perspective. Specifically, PTSD can be conceptualized as a disorder of fear and stress dysregulation, and the neural circuitry underlying these pathways in both animals and humans are becoming increasingly well understood. Furthermore, PTSD is the only disorder in psychiatry in which the initiating factor, the trauma exposure, can be identified. Thus, the pathophysiology of the fear and stress response underlying PTSD can be examined and potentially interrupted. Twin studies have shown that the development of PTSD following a trauma is heritable, and that genetic risk factors may account for up to 30-40% of this heritability. A current goal is to understand the gene pathways that are associated with PTSD, and how those genes act on the fear/stress circuitry to mediate risk vs. resilience for PTSD. This review will examine gene pathways that have recently been analysed, primarily through candidate gene studies (including neuroimaging studies of candidate genes), in addition to genome-wide associations and the epigenetic regulation of PTSD. Future and on-going studies are utilizing larger and collaborative cohorts to identify novel gene candidates through genome-wide association and other powerful genomic approaches. Identification of PTSD biological pathways strengthens the hope of progress in the mechanistic understanding of a model psychiatric disorder and allows for the development of targeted treatments and interventions.

  8. Posttraumatic stress disorder: a history and a critique.

    PubMed

    Andreasen, Nancy C

    2010-10-01

    Although posttraumatic stress disorder (PTSD) is sometimes considered to be a relatively new diagnosis, as the name first appeared in 1980, the concept of the disorder has a very long history. That history has often been linked to the history of war, but the disorder has also been frequently described in civilian settings involving natural disasters, mass catastrophes, and serious accidental injuries. The diagnosis first appeared in the official nomenclature when Diagnostic and Statistical Manual of Mental Disorders (DSM)-I was published in 1952 under the name gross stress reaction. It was omitted, however, in the next edition in 1968, after a long period of relative peace. When DSM-III was developed in the mid-1980s the recent occurrence of the Vietnam War provoked a more thorough examination of the disorder. PTSD was defined as a stress disorder that is a final common pathway occurring as a consequence of many different types of stressors, including both combat and civilian stress. The definition of PTSD has filled an important niche in clinical psychiatry. Its definition continues to raise important questions about the relationship between a stressor, the individual experiencing it, and the characteristic symptoms. © 2010 Association for Research in Nervous and Mental Disease.

  9. Genetic approaches to understanding post-traumatic stress disorder

    PubMed Central

    Almli, Lynn M.; Fani, Negar; Smith, Alicia K.; Ressler, Kerry J.

    2015-01-01

    Post-traumatic stress disorder (PTSD) is increasingly recognized as both a disorder of enormous mental health and societal burden, but also as an anxiety disorder that may be particularly understandable from a scientific perspective. Specifically, PTSD can be conceptualized as a disorder of fear and stress dysregulation, and the neural circuitry underlying these pathways in both animals and humans are becoming increasingly well understood. Furthermore, PTSD is the only disorder in psychiatry in which the initiating factor, the trauma exposure, can be identified. Thus, the pathophysiology of the fear and stress response underlying PTSD can be examined and potentially interrupted. Twin studies have shown that the development of PTSD following a trauma is heritable, and that genetic risk factors may account for up to 30–40% of this heritability. A current goal is to understand the gene pathways that are associated with PTSD, and how those genes act on the fear/stress circuitry to mediate risk vs. resilience for PTSD. This review will examine gene pathways that have recently been analysed, primarily through candidate gene studies (including neuroimaging studies of candidate genes), in addition to genome-wide associations and the epigenetic regulation of PTSD. Future and on-going studies are utilizing larger and collaborative cohorts to identify novel gene candidates through genome-wide association and other powerful genomic approaches. Identification of PTSD biological pathways strengthens the hope of progress in the mechanistic understanding of a model psychiatric disorder and allows for the development of targeted treatments and interventions. PMID:24103155

  10. Chronic Stress Alters Neural Activity in Medial Prefrontal Cortex During Retrieval of Extinction

    PubMed Central

    Wilber, Aaron A.; Walker, Adam G.; Southwood, Christopher J.; Farrell, Mollee R.; Lin, Grant L.; Rebec, George V.; Wellman, Cara L.

    2010-01-01

    Chronic restraint stress produces morphological changes in medial prefrontal cortex and disrupts a prefrontally mediated behavior, retrieval of extinction. To assess potential physiological correlates of these alterations, we compared neural activity in infralimbic and prelimbic cortex of unstressed versus stressed rats during fear conditioning and extinction. After implantation of microwire bundles into infralimbic or prelimbic cortex, rats were either unstressed or stressed via placement in a plastic restrainer (3 h/day for 1 week). Rats then underwent fear conditioning and extinction while activity of neurons in infralimbic or prelimbic cortex was recorded. Percent freezing and neural activity were assessed during all phases of training. Chronic stress enhanced freezing during acquisition of conditioned fear, and altered both prelimbic and infralimbic activity during this phase. Stress did not alter initial extinction or conditioned stimulus (CS)-related activity during this phase. However, stress impaired retrieval of extinction assessed 24 h later, and this was accompanied by alterations in neuronal activity in both prelimbic and infralimbic cortex. In prelimbic cortex, unstressed rats showed decreased activity in response to CS presentation, whereas stressed rats showed no change. In infralimbic cortex, neurons in unstressed rats exhibited increased firing in response to the CS, whereas stressed rats showed no increase in infralimbic firing during the tone. Finally, CS-related firing in infralimbic but not prelimbic cortex was correlated with extinction retrieval. Thus, the stress-induced alteration of neuronal activity in infralimbic cortex may be responsible for the stress-induced deficit in retrieval of extinction. PMID:21044660

  11. Effects of cortisol on cognition in major depressive disorder, posttraumatic stress disorder and borderline personality disorder - 2014 Curt Richter Award Winner.

    PubMed

    Wingenfeld, Katja; Wolf, Oliver T

    2015-01-01

    Stress hormones influence a wide range of cognitive functions, including memory performance and executive function. It is well established that glucocorticoids enhance memory consolidation but impair memory retrieval. While most of the effects have been attributed to glucocorticoid receptors (GR), the importance of mineralocorticoid receptors (MR) has been also emphasized. Dysfunctions in hypothalamic-pituitary-adrenal (HPA) axis have been reported for several mental disorders. While major depressive disorder (MDD) as well as borderline personality disorder (BPD) seem to be characterized by enhanced cortisol release in concert with a reduced feedback sensitivity of the HPA axis, in posttraumatic stress disorder (PTSD) a contrary picture has been reported. Despite the fact that altered GR function has been discussed for these disorders only very few studies have investigated the effects of glucocorticoids on cognitive performance in these patients so far. In a series of studies, we investigated the effects of glucocorticoids on cognition (i.e. declarative memory, working memory and response inhibition) in different mental disorders such as MDD, PTSD and BPD. While in patients with MDD cortisol administration failed to effect memory retrieval, patients with PTSD and BPD showed enhanced rather than impaired memory retrieval after cortisol administration. These results indicate an altered sensitivity to cortisol in these disorders. Results from one of our recent studies in the field of social cognition underline the importance of the MR. We found that emotional empathy was enhanced through stimulation of the MR via fludrocortisone in healthy participants and women with BPD. This review aims to integrate these findings and discuss potential mechanisms and implications.

  12. Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group.

    PubMed

    Schmaal, L; Veltman, D J; van Erp, T G M; Sämann, P G; Frodl, T; Jahanshad, N; Loehrer, E; Tiemeier, H; Hofman, A; Niessen, W J; Vernooij, M W; Ikram, M A; Wittfeld, K; Grabe, H J; Block, A; Hegenscheid, K; Völzke, H; Hoehn, D; Czisch, M; Lagopoulos, J; Hatton, S N; Hickie, I B; Goya-Maldonado, R; Krämer, B; Gruber, O; Couvy-Duchesne, B; Rentería, M E; Strike, L T; Mills, N T; de Zubicaray, G I; McMahon, K L; Medland, S E; Martin, N G; Gillespie, N A; Wright, M J; Hall, G B; MacQueen, G M; Frey, E M; Carballedo, A; van Velzen, L S; van Tol, M J; van der Wee, N J; Veer, I M; Walter, H; Schnell, K; Schramm, E; Normann, C; Schoepf, D; Konrad, C; Zurowski, B; Nickson, T; McIntosh, A M; Papmeyer, M; Whalley, H C; Sussmann, J E; Godlewska, B R; Cowen, P J; Fischer, F H; Rose, M; Penninx, B W J H; Thompson, P M; Hibar, D P

    2016-06-01

    The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen's d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen's d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.

  13. Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group

    PubMed Central

    Schmaal, L; Veltman, D J; van Erp, T G M; Sämann, P G; Frodl, T; Jahanshad, N; Loehrer, E; Tiemeier, H; Hofman, A; Niessen, W J; Vernooij, M W; Ikram, M A; Wittfeld, K; Grabe, H J; Block, A; Hegenscheid, K; Völzke, H; Hoehn, D; Czisch, M; Lagopoulos, J; Hatton, S N; Hickie, I B; Goya-Maldonado, R; Krämer, B; Gruber, O; Couvy-Duchesne, B; Rentería, M E; Strike, L T; Mills, N T; de Zubicaray, G I; McMahon, K L; Medland, S E; Martin, N G; Gillespie, N A; Wright, M J; Hall, G B; MacQueen, G M; Frey, E M; Carballedo, A; van Velzen, L S; van Tol, M J; van der Wee, N J; Veer, I M; Walter, H; Schnell, K; Schramm, E; Normann, C; Schoepf, D; Konrad, C; Zurowski, B; Nickson, T; McIntosh, A M; Papmeyer, M; Whalley, H C; Sussmann, J E; Godlewska, B R; Cowen, P J; Fischer, F H; Rose, M; Penninx, B W J H; Thompson, P M; Hibar, D P

    2016-01-01

    The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=−0.14, % difference=−1.24). This effect was driven by patients with recurrent MDD (Cohen's d=−0.17, % difference=−1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=−0.20, % difference=−1.85) and a trend toward smaller amygdala (Cohen's d=−0.11, % difference=−1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status. PMID:26122586

  14. Does posttraumatic stress disorder (PTSD) affect performance?

    PubMed

    LeBlanc, Vicki R; Regehr, Cheryl; Jelley, R Blake; Barath, Irene

    2007-08-01

    Research has increasingly identified alarming levels of traumatic stress symptoms in individuals working in emergency services and other high stress jobs. This study examined the effects of prior critical incident exposure and current posttraumatic symptoms on the performance of a nonpatient population, police recruits, during an acutely stressful event. A stressful policing situation was created through the use of a video simulator room that was responsive to actions of participants. The performance of participants to the simulated emergency was evaluated by 3 independent blinded raters. Prior exposure to critical incidents was measured using the Critical Incident History Questionnaire and current level of traumatic stress symptoms was measured using the Impact of Events Scale-Revised. Neither previous exposure to critical incidents nor trauma symptoms correlated with performance level. Recruits with high or severe levels of trauma symptoms did not demonstrate impairments in judgment, communication, or situation control compared with their colleagues with lesser or no trauma symptoms. On the basis of these findings, there is no reason to believe that police recruits with PTSD are prone to making errors of communication or judgment that would place them or others at increased risk.

  15. The Genetics of Stress-Related Disorders: PTSD, Depression, and Anxiety Disorders.

    PubMed

    Smoller, Jordan W

    2016-01-01

    Research into the causes of psychopathology has largely focused on two broad etiologic factors: genetic vulnerability and environmental stressors. An important role for familial/heritable factors in the etiology of a broad range of psychiatric disorders was established well before the modern era of genomic research. This review focuses on the genetic basis of three disorder categories-posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and the anxiety disorders-for which environmental stressors and stress responses are understood to be central to pathogenesis. Each of these disorders aggregates in families and is moderately heritable. More recently, molecular genetic approaches, including genome-wide studies of genetic variation, have been applied to identify specific risk variants. In this review, I summarize evidence for genetic contributions to PTSD, MDD, and the anxiety disorders including genetic epidemiology, the role of common genetic variation, the role of rare and structural variation, and the role of gene-environment interaction. Available data suggest that stress-related disorders are highly complex and polygenic and, despite substantial progress in other areas of psychiatric genetics, few risk loci have been identified for these disorders. Progress in this area will likely require analysis of much larger sample sizes than have been reported to date. The phenotypic complexity and genetic overlap among these disorders present further challenges. The review concludes with a discussion of prospects for clinical translation of genetic findings and future directions for research.

  16. Forced swimming stress induced alterations in ingestive behavior in rats.

    PubMed

    Nagaraja, H S; Jeganathan, P S

    2003-01-01

    The effects of forced swimming stress (15 minutes per day) on body weight, food intake, blood sugar, water intake, and urine output were studied in adult male Wistar rats on the first, seventh, fourteenth and 21st days in different subgroups. There was a significant initial decrease in the body weight up to 14 days followed by a regain in the body weight, which was sustained until 21 days. Though there was no change in the food intake initially for 7 days, after 14 days a significant increase in the food intake was observed. A significant hypoglycemia was observed throughout the entire period of stress. More significant fall in the blood sugar level was observed in the initial period of exposure of stress (1-7 days). There was a significant reduction in the water intake in the stressed animals. Urine output decreased significantly up to 7 days of stress, though it got marginally increased later. Thus, repeated stress may produce a reduction in body weight only initially, which is accompanied with an initial decrease in food and water intake also. The peak response to stress was seen after 7 days of stress exposure. There was a gradual recovery back to normal in the body weight, food intake, and water intake and urine output when stress period was prolonged to 14-21 days. This is suggestive of the adaptation of the organism to repeated exposure of similar kind of stress.

  17. Acute stress alters transcript expression pattern and reduces processing of proBDNF to mature BDNF in Dicentrarchus labrax

    PubMed Central

    2010-01-01

    Background Stress involves alterations of brain functioning that may precipitate to mood disorders. The neurotrophin Brain Derived Neurotrophic Factor (BDNF) has recently been involved in stress-induced adaptation. BDNF is a key regulator of neuronal plasticity and adaptive processes. Regulation of BDNF is complex and may reflect not only stress-specific mechanisms but also hormonal and emotional responses. For this reason we used, as an animal model of stress, a fish whose brain organization is very similar to that of higher vertebrates, but is generally considered free of emotional reactions. Results We provide a comprehensive characterization of BDNF gene in the Dicentrarchus labrax and its transcriptional, translational and post-translational regulation following acute stress. While total BDNF mRNA levels are unchanged, BDNF transcripts 1c and 1d resulted down regulated after acute stress. Acute stress induces also a significant increase in proBDNF levels and reduction in mature BDNF suggesting altered regulation of proBDNF proteolytic processing. Notably, we provide here the first evidence that fishes possess a simplified proteolytic regulation of BDNF since the pro28Kda form, generated by the SKI-1 protease in mammals, is absent in fishes because the cleavage site has first emerged in reptilians. Finally, we show that the proBDNF/totBDNF ratio is a highly predictive novel quantitative biomarker to detect stress in fishes with sensitivity = 100%, specificity = 87%, and Negative Predictive Value = 100%. Conclusion The high predictivity of proBDNF/totBDNF ratio for stress in lower vertebrates indicates that processing of BDNF is a central mechanism in adaptation to stress and predicts that a similar regulation of pro/mature BDNF has likely been conserved throughout evolution of vertebrates from fish to man. PMID:20074340

  18. Acute stress alters transcript expression pattern and reduces processing of proBDNF to mature BDNF in Dicentrarchus labrax.

    PubMed

    Tognoli, Chiara; Rossi, Federica; Di Cola, Francesco; Baj, Gabriele; Tongiorgi, Enrico; Terova, Genciana; Saroglia, Marco; Bernardini, Giovanni; Gornati, Rosalba

    2010-01-14

    Stress involves alterations of brain functioning that may precipitate to mood disorders. The neurotrophin Brain Derived Neurotrophic Factor (BDNF) has recently been involved in stress-induced adaptation. BDNF is a key regulator of neuronal plasticity and adaptive processes. Regulation of BDNF is complex and may reflect not only stress-specific mechanisms but also hormonal and emotional responses. For this reason we used, as an animal model of stress, a fish whose brain organization is very similar to that of higher vertebrates, but is generally considered free of emotional reactions. We provide a comprehensive characterization of BDNF gene in the Dicentrarchus labrax and its transcriptional, translational and post-translational regulation following acute stress. While total BDNF mRNA levels are unchanged, BDNF transcripts 1c and 1d resulted down regulated after acute stress. Acute stress induces also a significant increase in proBDNF levels and reduction in mature BDNF suggesting altered regulation of proBDNF proteolytic processing. Notably, we provide here the first evidence that fishes possess a simplified proteolytic regulation of BDNF since the pro28Kda form, generated by the SKI-1 protease in mammals, is absent in fishes because the cleavage site has first emerged in reptilians. Finally, we show that the proBDNF/totBDNF ratio is a highly predictive novel quantitative biomarker to detect stress in fishes with sensitivity = 100%, specificity = 87%, and Negative Predictive Value = 100%. The high predictivity of proBDNF/totBDNF ratio for stress in lower vertebrates indicates that processing of BDNF is a central mechanism in adaptation to stress and predicts that a similar regulation of pro/mature BDNF has likely been conserved throughout evolution of vertebrates from fish to man.

  19. Conduct Disorder, War Zone Stress, and War-Related Posttraumatic Stress Disorder Symptoms In American Indian Vietnam Veterans

    PubMed Central

    Dillard, Denise; Jacobsen, Clemma; Ramsey, Scott; Manson, Spero

    2008-01-01

    This study examined whether conduct disorder (CD) was associated with war zone stress and war-related post-traumatic stress disorder (PTSD) symptoms in American Indian (AI) Vietnam veterans. Cross-sectional lay-interview data was analyzed for 591 male participants from the American Indian Vietnam Veterans Project. Logistic regression evaluated the association of CD with odds of high war zone stress and linear regression evaluated the association of CD and PTSD symptom severity. Childhood CD was not associated with increased odds of high war zone stress. CD was associated with elevated war-related PTSD symptoms among male AI Vietnam Veterans independent of war zone stress level and other mediators. Future efforts should examine reasons for this association and whether the association exists in other AI populations. PMID:17343265

  20. Musculoskeletal disorders and stress among footwear industry workers.

    PubMed

    de Almeida, Larissa Brentini; Vieira, Edgar Ramos; Zaia, José Eduardo; de Oliveira Santos, Branca Maria; Lourenço, Américo Riccardi Vaccari; Quemelo, Paulo Roberto Veiga

    2017-01-01

    Manufacturing footwear requires intense manual labor and high repetitions with low variability in function that may lead to musculoskeletal disorders (MSD) symptoms and psychological stress. To evaluate a potential association between musculoskeletal disorders (MSD) and perceived stress among footwear industry workers. The Nordic General Questionnaire (NGQ) and the Perceived Stress Scale (PSS-10) were completed by 357 footwear industry workers. The association between MSD and perceived stress was evaluated using the Chi-Square test and Odds Ratios along with their 95% Confidence Interval (95% CI) were calculated. The twelve-month prevalence of MSD symptoms among the respondents was 66% (n = 236) and the symptoms were significantly associated with perceived stress (p = 0.002, OR: 10, 95% CI: 1.7 to 60.6). The seven-day prevalence of MSD symptoms was 33% and the symptoms were also significantly associated with perceived stress (p = 0.001, OR: 2.7, 95% CI:0.8 to 9.3). The association between perceived stress and MSD symptoms indicates a strong association between MSD symptoms and perceived stress levels. Considering that these problems are important determinants of worker's health, a combined approach to reduce both stress and MSD symptoms is necessary for prevention and health promotion in the footwear industry.

  1. Clinical outcomes associated with comorbid posttraumatic stress disorder among patients with bipolar disorder.

    PubMed

    Passos, Ives C; Jansen, Karen; Cardoso, Taiane de A; Colpo, Gabriela D; Zeni, Cristian P; Quevedo, Joao; Kauer-Sant'Anna, Márcia; Zunta-Soares, Giovanna; Soares, Jair C; Kapczinski, Flavio

    2016-05-01

    To assess clinical outcomes associated with the presence of a lifetime history of comorbid posttraumatic stress disorder in subjects with bipolar disorder. This cross-sectional study of 284 subjects with bipolar disorder (DSM-IV) assessed the association between lifetime comorbid posttraumatic stress disorder (DSM-IV) and clinical characteristics. Participants were included from January 2006 to June 2009. We assessed age at onset, number of mood episodes, presence of rapid cycling, first drug use, suicide attempts, hospitalizations, functional impairment, and quality of life. Diagnostic, clinical, and functional assessments were carried out using the Structured Clinical Interview for DSM-IV Axis I Disorders, patient edition (SCID-I/P), the Functioning Assessment Short Test, and the World Health Organization Quality of Life scale. The number of manic episodes as assessed by SCID-I/P was the primary outcome. The prevalence of lifetime comorbid posttraumatic stress disorder was 19.7% (56 subjects). Subjects with bipolar disorder and posttraumatic stress disorder had an accelerated course of illness, with a lower age at onset of manic/hypomanic episodes (P = .009) and earlier initiation of illicit drug use (P = .008). In addition, they were more likely to be younger when they received the diagnosis of bipolar disorder (P = .036) and had a higher number of manic/hypomanic episodes (P = .01). Quality of life was worse in all domains among subjects who presented the comorbidity, and rates of functional impairment were higher. Comorbid posttraumatic stress disorder was associated with increased morbidity and accelerated illness progression among subjects with bipolar disorder. © Copyright 2016 Physicians Postgraduate Press, Inc.

  2. [Stress-induced alteration of the antiaggressive effect of anxiolytics].

    PubMed

    Molodavkin, G M; Voronina, T A; Aldarmaa, Zh; Meletova, O K

    2004-01-01

    The influence of stresses of various etiology (prolonged isolation, inescapable electrostimulation) on the antiaggressive effect of anxiolytics was studied in outbread white male rats. It was established that, in contrast to the anticonflict effect (decreasing under the action of stress), then antiaggressive action of the drugs studied (diazepam, phenazepam, clonazepam, alprazolam) exhibits qualitative changes. In the absence of stress, the threshold of aggressive reaction is low and anxiolytics increase this level. Under the action of stress, the threshold of aggressive reaction increases, and the same drugs reduce this threshold to the normal level, thus producing proaggressive action. The degree of changes and the rate of restoration of the initial activity depend on the efficacy of anxiolytics, the strength and duration of stress, and on the duration of drug administration during the stress aftereffect. A possible mechanism of this phenomenon can be the interaction of the GABA-benzodiazepine and opiate endogenous systems.

  3. Vulnerability of conditional NCAM-deficient mice to develop stress-induced behavioral alterations.

    PubMed

    Bisaz, Reto; Sandi, Carmen

    2012-03-01

    Previous studies in rodents showed that chronic stress induces structural and functional alterations in several brain regions, including shrinkage of the hippocampus and the prefrontal cortex, which are accompanied by cognitive and emotional disturbances. Reduced expression of the neural cell adhesion molecule (NCAM) following chronic stress has been proposed to be crucially involved in neuronal retraction and behavioral alterations. Since NCAM gene polymorphisms and altered expression of alternatively spliced NCAM isoforms have been associated with bipolar depression and schizophrenia in humans, we hypothesized that reduced expression of NCAM renders individuals more vulnerable to the deleterious effects of stress on behavior. Here, we specifically questioned whether mice in which the NCAM gene is inactivated in the forebrain by cre-recombinase under the control of the calcium-calmodulin-dependent kinase II promoter (conditional NCAM-deficient mice), display increased vulnerability to stress. We assessed the evolving of depressive-like behaviors and spatial learning and memory impairments following a subchronic stress protocol (2 weeks) that does not result in behavioral dysfunction, nor in altered NCAM expression, in wild-type mice. Indeed, while no behavioral alterations were detected in wild-type littermates after subchronic stress, conditional NCAM-deficient mice showed increased immobility in the tail suspension test and deficits in reversal spatial learning in the water maze. These findings indicate that diminished NCAM expression might be a critical vulnerability factor for the development of behavioral alterations by stress and further support a functional involvement of NCAM in stress-induced cognitive and emotional disturbances.

  4. Anticonvulsants to treat post-traumatic stress disorder.

    PubMed

    Wang, Hee Ryung; Woo, Young Sup; Bahk, Won-Myong

    2014-09-01

    We reviewed the existing literature on the efficacy of anticonvulsants in treating post-traumatic stress disorder. We performed a literature search using PubMed, EMBASE and the Cochrane database on 30 September 2013. Randomized,controlled studies that investigated the efficacy of anticonvulsants for post-traumatic stress disorder were included in this review. Studies with retrospective designs, case reports and case series were excluded. A total of seven studies met the inclusion criteria for this review. Three studies used topiramate with negative findings regarding its efficacy. Two studies used divalproex, both of which failed to show superiority over placebo. One study used lamotrigine, with favourable results, and one study used tiagabine, with negative results. Future long-term studies with larger sample sizes are needed to investigate the clinical utility of anticonvulsants for posttraumatic stress disorder treatment.

  5. Associations between Prolonged Grief Disorder, Depression, Posttraumatic Stress Disorder, and Anxiety in Rwandan Genocide Survivors

    ERIC Educational Resources Information Center

    Schaal, Susanne; Dusingizemungu, Jean-Pierre; Jacob, Nadja; Neuner, Frank; Elbert, Thomas

    2012-01-01

    A number of studies have demonstrated that symptoms of prolonged grief disorder (PGD) represent a symptom cluster distinct from bereavement-related depression, anxiety, and posttraumatic stress disorder (PTSD). The aim of the present study was to confirm and extend these findings using the most recent criteria defining PGD. The authors interviewed…

  6. Posttraumatic Stress Disorder in Individuals with Diagnosis of Autistic Spectrum Disorders

    ERIC Educational Resources Information Center

    Mehtar, Mohamad; Mukaddes, Nahit Motavalli

    2011-01-01

    Although children and adolescents with developmental disabilities are said to have higher risks of abuse than those without, trauma and Posttraumatic Stress Disorder (PTSD) are little examined in those diagnosed with Autistic Spectrum Disorders (ASDs). Our study aims to assess trauma types, prevalence, risk factors and symptoms; and PTSD in…

  7. Behavioral Activation in the Treatment of Comorbid Posttraumatic Stress Disorder and Major Depressive Disorder

    ERIC Educational Resources Information Center

    Mulick, Patrick S.; Naugle, Amy E.

    2009-01-01

    This study investigated the efficacy of 10-weeks of Behavioral Activation (BA) in the treatment of comorbid Post-traumatic Stress Disorder (PTSD) and Major Depressive Disorder (MDD) in four adults using a nonconcurrent multiple baseline across participants design. All participants met full "DSM-IV" criteria for both MDD and PTSD at the…

  8. Associations between Prolonged Grief Disorder, Depression, Posttraumatic Stress Disorder, and Anxiety in Rwandan Genocide Survivors

    ERIC Educational Resources Information Center

    Schaal, Susanne; Dusingizemungu, Jean-Pierre; Jacob, Nadja; Neuner, Frank; Elbert, Thomas

    2012-01-01

    A number of studies have demonstrated that symptoms of prolonged grief disorder (PGD) represent a symptom cluster distinct from bereavement-related depression, anxiety, and posttraumatic stress disorder (PTSD). The aim of the present study was to confirm and extend these findings using the most recent criteria defining PGD. The authors interviewed…

  9. Autism Spectrum Disorder and Fetal Alcohol Spectrum Disorder. Part I: A Comparison of Parenting Stress

    ERIC Educational Resources Information Center

    Watson, Shelley L.; Coons, Kelly D.; Hayes, Stephanie A.

    2013-01-01

    Background: There is a long history of research on parents of children with disabilities, but to the authors' knowledge, no study has compared the stress of parents of children with fetal alcohol spectrum disorder (FASD) to parents of children with autism spectrum disorder (ASD). Method: Twenty-five parents of children with ASD and 25 parents of…

  10. Posttraumatic Stress Disorder in Individuals with Diagnosis of Autistic Spectrum Disorders

    ERIC Educational Resources Information Center

    Mehtar, Mohamad; Mukaddes, Nahit Motavalli

    2011-01-01

    Although children and adolescents with developmental disabilities are said to have higher risks of abuse than those without, trauma and Posttraumatic Stress Disorder (PTSD) are little examined in those diagnosed with Autistic Spectrum Disorders (ASDs). Our study aims to assess trauma types, prevalence, risk factors and symptoms; and PTSD in…

  11. Personality Disorders, Coping Strategies, and Posttraumatic Stress Disorder in Women with Histories of Childhood Sexual Abuse

    ERIC Educational Resources Information Center

    Johnson, Dawn M.; Sheahan, Timothy C.; Chard, Kathleen M.

    2003-01-01

    Using a treatment-seeking sample of adult female survivors of childhood sexual abuse, the relationships between coping strategies, personality disorders (PD) and Posttraumatic Stress Disorder (PTSD) were explored. A variety of PDs were found to exist in this population, with avoidant, antisocial, dependent PDs having higher frequencies than…

  12. Autism Spectrum Disorder and Fetal Alcohol Spectrum Disorder. Part I: A Comparison of Parenting Stress

    ERIC Educational Resources Information Center

    Watson, Shelley L.; Coons, Kelly D.; Hayes, Stephanie A.

    2013-01-01

    Background: There is a long history of research on parents of children with disabilities, but to the authors' knowledge, no study has compared the stress of parents of children with fetal alcohol spectrum disorder (FASD) to parents of children with autism spectrum disorder (ASD). Method: Twenty-five parents of children with ASD and 25 parents of…

  13. Induction of oxidative stress causes functional alterations in mouse urothelium via a TRPM8-mediated mechanism: implications for aging.

    PubMed

    Nocchi, Linda; Daly, Donna M; Chapple, Christopher; Grundy, David

    2014-06-01

    The incidence of bladder conditions such as overactive bladder syndrome and its associated urinary incontinence is highly prevalent in the elderly. However, the mechanisms underlying these disorders are unclear. Studies suggest that the urothelium forms a 'sensory network' with the underlying innervation, alterations in which, could compromise bladder function. As the accumulation of reactive oxygen species can cause functional alterations with age, the aim of this study was to investigate whether oxidative stress alters urothelial sensory signalling and whether the mechanism underlying the effect of oxidative stress on the urothelium plays a role in aging. Five-month-old(young) and 24-month-old (aged) mice were used. H2O2 , used to induce oxidative stress, resulted in an increase in bladder afferent nerve activity and urothelial intracellular calcium in preparations from young mice. These functional changes were concurrent with upregulation of TRPM8 in the urothelium. Moreover, application of a TRPM8 antagonist significantly attenuated the H2O2 -induced calcium responses. Interestingly, an upregulation of TRPM8 was also found in the urothelium from aged mice, where high oxidative stress levels were observed, together with a greater calcium response to the TRPM8 agonist WS12. Furthermore, these calcium responses were attenuated by pretreatment with the antioxidant N-acetyl-cysteine. This study shows that oxidative stress affects urothelial function involving a TRPM8-mediated mechanism and these effects may have important implications for aging. These data provide an insight into the possible mechanisms by which oxidative stress causes physiological alterations in the bladder, which may also occur in other organs susceptible to aging.

  14. Post Traumatic Stress Disorder: The Facts

    DTIC Science & Technology

    2007-02-22

    the medical professionals used to believe that Soldiers who tend to be emotionally numb after a trauma were showing a healthy response, but now...stress. Some studies have shown that cortisol levels are lower than normal and epinephrine and norepinephrine are higher than normal. 3. When

  15. [Relationship between posttraumatic stress disorder, personality disorders, and personal history in a postraumatic unit (descriptive study)].

    PubMed

    Spinetto, Marcela; Larregina, Luciana; Benvenuto, Cecilia

    2007-01-01

    In examining predictors of Posttraumatic Stress Disorders, researchers have focused on trauma intensity, symptoms severity, personality disorders and devoted less attention to other variables. This descriptive study examine how personality disorders, intensity of trauma and demographic variables (previous trauma and vulnerability) are related to the likelihood of experiencing a trauma, and to the severity of posttraumatic symptoms in a sample of 50 patients reporting a wide range of trauma.

  16. Animal models of post-traumatic stress disorder and recent neurobiological insights.

    PubMed

    Whitaker, Annie M; Gilpin, Nicholas W; Edwards, Scott

    2014-09-01

    Post-traumatic stress disorder (PTSD) is a complex psychiatric disorder characterized by the intrusive re-experiencing of past trauma, avoidant behavior, enhanced fear, and hyperarousal following a traumatic event in vulnerable populations. Preclinical animal models do not replicate the human condition in its entirety, but seek to mimic symptoms or endophenotypes associated with PTSD. Although many models of traumatic stress exist, few adequately capture the complex nature of the disorder and the observed individual variability in susceptibility of humans to PTSD. In addition, various types of stressors may produce different molecular neuroadaptations that likely contribute to the various behavioral disruptions produced by each model, although certain consistent neurobiological themes related to PTSD have emerged. For example, animal models report traumatic stress-induced and trauma reminder-induced alterations in neuronal activity in the amygdala and prefrontal cortex, in agreement with the human PTSD literature. Models have also provided a conceptual framework for the often-observed combination of PTSD and comorbid conditions such as alcohol use disorder. Future studies will continue to refine preclinical PTSD models in hope of capitalizing on their potential to deliver new and more efficacious treatments for PTSD and associated psychiatric disorders.

  17. Animal Models of Post-Traumatic Stress Disorder and Recent Neurobiological Insights

    PubMed Central

    Whitaker, Annie M.; Gilpin, Nicholas W.; Edwards, Scott

    2014-01-01

    Post-traumatic stress disorder (PTSD) is a complex psychiatric disorder characterized by the intrusive re-experiencing of past trauma, avoidant behavior, enhanced fear, and hyperarousal following a traumatic event in vulnerable populations. Preclinical animal models do not replicate the human condition in its entirety, but seek to mimic symptoms or endophenotypes associated with PTSD. Although many models of traumatic stress exist, few adequately capture the complex nature of the disorder and the observed individual variability in susceptibility of humans to develop PTSD. In addition, various types of stressors may produce different molecular neuroadaptations that likely contribute to the various behavioral disruptions produced by each model, although certain consistent neurobiological themes related to PTSD have emerged. For example, animal models report traumatic stress- and trauma reminder-induced alterations in neuronal activity in the amygdala and prefrontal cortex, in agreement with the human PTSD literature. Models have also provided a conceptual framework for the often observed combination of PTSD and co-morbid conditions such as alcohol use disorder (AUD). Future studies will continue to refine preclinical PTSD models in hopes of capitalizing on their potential to deliver new and more efficacious treatments for PTSD and associated psychiatric disorders. PMID:25083568

  18. Written Disclosure Treatment for Posttraumatic Stress Disorder in Substance Use Disorder Inpatients

    ERIC Educational Resources Information Center

    Bragdon, Rodney A.; Lombardo, Thomas W.

    2012-01-01

    Comprehensive exposure-based approaches to treating posttraumatic stress disorder (PTSD) are effective, but they are time intensive and not widely used because of factors such as client noncompliance and fears of iatrogenic effects. Exposure by writing disclosure (WD), modeled after Pennebaker's brief stress-reduction procedure, may circumvent…

  19. Written Disclosure Treatment for Posttraumatic Stress Disorder in Substance Use Disorder Inpatients

    ERIC Educational Resources Information Center

    Bragdon, Rodney A.; Lombardo, Thomas W.

    2012-01-01

    Comprehensive exposure-based approaches to treating posttraumatic stress disorder (PTSD) are effective, but they are time intensive and not widely used because of factors such as client noncompliance and fears of iatrogenic effects. Exposure by writing disclosure (WD), modeled after Pennebaker's brief stress-reduction procedure, may circumvent…

  20. Posttraumatic stress disorder and depression as comorbid disorders.

    PubMed

    Ljubicić, Dulijano; Peitl, Marija Vucić; Peitl, Vjekoslav; Ljubicić, Rudolf; Filipović, Biljana

    2009-09-01

    Depression is the most frequent disorder of today. It is unique for the fact that it can become a comorbid illness with almost any other psychiatric disorder. Premorbid depression is also a risk factor for the development of PTSD, while at the same time traumatic experience is a risk factor for the development of depression. These facts show us that a close connection between these two diagnostic entities exists. Aim of this research was to analyze the levels of depressiveness in patients that were hospitalized and patients that were treated in the Day hospital. Also, to establish the connection of age, time spent in combat (war), length of treatment and number of hospitalizations with the results from the Beck's depression inventory. Participants were divided into two groups, 36 patients that were treated for PTSD in a hospital setting and 64 patients that were treated in the Day hospital. Participants completed Beck's self-evaluation inventory for depression, as it assesses the degree of depression. Two groups did not differ regarding to age, time spent in combat (war), the length of treatment and level of depressiveness assessed by Beck's depression inventory. Score on Beck's depression inventory was significantly positively correlated with the age of participants and the number of hospitalizations. Older participants and participants that were hospitalized more often score higher on Beck's depression inventory. Results show that there is no difference between the two groups of participants of differing levels of depressiveness, but depression most often presents as severe depression in both groups of participants. Older participants and participants that were hospitalized more often are more depressed. This research points to the fact that it is necessary to treat PTSD and depression at the same time, because parallel treatment of these comorbid disorders leads to a decrease of the rate of suicide, due to the fact that depression is often the leading cause of

  1. Neuromodulator and Emotion Biomarker for Stress Induced Mental Disorders

    PubMed Central

    Gu, Simeng; Wang, Wei; Huang, Jason H.

    2016-01-01

    Affective disorders are a leading cause of disabilities worldwide, and the etiology of these many affective disorders such as depression and posttraumatic stress disorder is due to hormone changes, which includes hypothalamus-pituitary-adrenal axis in the peripheral nervous system and neuromodulators in the central nervous system. Consistent with pharmacological studies indicating that medical treatment acts by increasing the concentration of catecholamine, the locus coeruleus (LC)/norepinephrine (NE) system is regarded as a critical part of the central “stress circuitry,” whose major function is to induce “fight or flight” behavior and fear and anger emotion. Despite the intensive studies, there is still controversy about NE with fear and anger. For example, the rats with LC ablation were more reluctant to leave a familiar place and took longer to consume the food pellets in an unfamiliar place (neophobia, i.e., fear in response to novelty). The reason for this discrepancy might be that NE is not only for flight (fear), but also for fight (anger). Here, we try to review recent literatures about NE with stress induced emotions and their relations with mental disorders. We propose that stress induced NE release can induce both fear and anger. “Adrenaline rush or norepinephrine rush” and fear and anger emotion might act as biomarkers for mental disorders. PMID:27051536

  2. Posttraumatic Stress Disorder, Exposure to Combat, and Lower Plasma Cortisol among Vietnam Veterans: Findings and Clinical Implications.

    ERIC Educational Resources Information Center

    Boscarino, Joseph A.

    1996-01-01

    Clinical studies suggest individuals with posttraumatic stress disorder (PSD) experience neuroendocrine systems alterations, resulting in significantly lower plasma cortisol. To test this hypothesis, morning serum cortisol was compared among a national sample of Vietnam "theater" veterans (n=2,490) and a sample of Vietnam "era"…

  3. Parenting Stress Among Caregivers of Children With Bipolar Spectrum Disorders.

    PubMed

    Perez Algorta, Guillermo; MacPherson, Heather A; Youngstrom, Eric A; Belt, Caroline C; Arnold, L Eugene; Frazier, Thomas W; Taylor, H Gerry; Birmaher, Boris; Horwitz, Sarah McCue; Findling, Robert L; Fristad, Mary A

    2017-02-26

    Caregivers of psychiatrically impaired children experience considerable parenting stress. However, no research has evaluated parenting stress within the context of pediatric bipolar spectrum disorders (BPSD). Thus, the aim of this investigation was to identify predictors and moderators of stress among caregivers in the Longitudinal Assessment of Manic Symptoms study. Participants included 640 children and their caregivers in the Longitudinal Assessment of Manic Symptoms cohort. Children had a mean age of 9.4 ± 1.9 years (68% male, 23% BPSD); parents had a mean age of 36.5 ± 8.3 years (84% mothers). Children with BPSD had more service utilization, psychiatric diagnoses, mood and anxiety symptoms, and functional impairment but fewer disruptive behavior disorders. Caregivers of children with BPSD were more likely than caregivers of children without BPSD to have a partner, elevated depressive symptoms, antisocial tendencies, and parenting stress (Cohen's d = .49). For the whole sample, higher child IQ, mania, anxiety, disruptive behavior, and caregiver depression predicted increased parenting stress; maternal conduct disorder predicted lower stress. Child anxiety and disruptive behavior were associated with elevated caregiver stress only for non-BPSD children. Caregivers of children with BPSD experience significant burden and thus require specialized, family-focused interventions. As stress was also elevated, to a lesser degree, among depressed caregivers of children with higher IQ, mania, anxiety, and disruptive behavior, these families may need additional supports as well. Although parents with conduct/antisocial problems evidenced lower stress, these difficulties should be monitored. Thus, parenting stress should be evaluated and addressed in the treatment of childhood mental health problems, especially BPSD.

  4. Acute stress disorder and the transition to post-traumatic stress disorder in children and adolescents: prevalence, course, prognosis, diagnostic suitability and risk markers

    PubMed Central

    Meiser-Stedman, Richard; McKinnon, Anna; Dixon, Clare; Boyle, Adrian; Smith, Patrick; Dalgleish, Tim

    2017-01-01

    Background Early recovery from trauma exposure in youth is poorly understood. This prospective longitudinal study examined the early course of traumatic stress responses in recently trauma-exposed youth; evaluated the revised DSM-5 acute stress disorder (ASD) and post-traumatic stress disorder (PTSD) diagnoses and alternative diagnoses; and identifed risk factors for persistent traumatic stress. Method Participants were 8-17 year old Emergency Departments attendees exposed to single incident traumas. Structured clinical interviews were undertaken at two (n=226) and nine weeks (n=208) post-trauma. Results Using the revised criteria in DSM-5, 14.2% met criteria for ASD at week 2 and 9.6% met criteria for PTSD at 9 weeks. These prevalences were similar to the corresponding DSM-IV diagnoses (18.6% ASD at week two; 8.7% PTSD at week nine). Using the same diagnostic criteria (DSM-IV or DSM-5) across assessments (i.e. ‘2 week PTSD’) suggested that caseness declined in prevalence by approximately half. Overlap between DSM-IV and DSM-5 ASD and DSM-5 preschool child PTSD diagnoses was considerable. Two diagnoses were strongly predictive of corresponding week nine diagnoses. Youth with ASD who subsequently had PTSD reported more negative alterations in cognition and mood at two-weeks than those youth who did not develop PTSD. Conclusions Youth exposed to single-event traumas experience considerable natural recovery in the first months post-trauma. Using DSM-5 criteria, ASD may not capture all clinically significant traumatic stress in the acute phase and is only moderately sensitive for later PTSD. Future research needs to address the role and etiology of negative alterations in cognition and mood symptoms. PMID:28135019

  5. The Genetics of Stress-Related Disorders: PTSD, Depression, and Anxiety Disorders

    PubMed Central

    Smoller, Jordan W

    2016-01-01

    Research into the causes of psychopathology has largely focused on two broad etiologic factors: genetic vulnerability and environmental stressors. An important role for familial/heritable factors in the etiology of a broad range of psychiatric disorders was established well before the modern era of genomic research. This review focuses on the genetic basis of three disorder categories—posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and the anxiety disorders—for which environmental stressors and stress responses are understood to be central to pathogenesis. Each of these disorders aggregates in families and is moderately heritable. More recently, molecular genetic approaches, including genome-wide studies of genetic variation, have been applied to identify specific risk variants. In this review, I summarize evidence for genetic contributions to PTSD, MDD, and the anxiety disorders including genetic epidemiology, the role of common genetic variation, the role of rare and structural variation, and the role of gene–environment interaction. Available data suggest that stress-related disorders are highly complex and polygenic and, despite substantial progress in other areas of psychiatric genetics, few risk loci have been identified for these disorders. Progress in this area will likely require analysis of much larger sample sizes than have been reported to date. The phenotypic complexity and genetic overlap among these disorders present further challenges. The review concludes with a discussion of prospects for clinical translation of genetic findings and future directions for research. PMID:26321314

  6. Posttraumatic stress disorder symptom trajectories in Hurricane Katrina affected youth.

    PubMed

    Self-Brown, Shannon; Lai, Betty S; Thompson, Julia E; McGill, Tia; Kelley, Mary Lou

    2013-05-01

    This study examined trajectories of posttraumatic stress disorder symptoms in Hurricane Katrina affected youth. A total of 426 youth (51% female; 8-16 years old; mean age=11 years; 75% minorities) completed assessments at 4 time points post-disaster. Measures included Hurricane impact variables (initial loss/disruption and perceived life threat); history of family and community violence exposure, parent and peer social support, and post-disaster posttraumatic stress symptoms. Latent class growth analysis demonstrated that there were three distinct trajectories of posttraumatic stress disorder symptoms identified for this sample of youth (resilient, recovering, and chronic, respectively). Youth trajectories were associated with Hurricane-related initial loss/disruption, community violence, and peer social support. The results suggest that youth exposed to Hurricane Katrina have variable posttraumatic stress disorder symptom trajectories. Significant risk and protective factors were identified. Specifically, youth Hurricane and community violence exposure increased risk for a more problematic posttraumatic stress disorder symptom trajectory, while peer social support served as a protective factor for these youth. Identification of these factors suggests directions for future research as well as potential target areas for screening and intervention with disaster exposed youth. The convenience sample limits the external validity of the findings to other disaster exposed youth, and the self-report data is susceptible to response bias. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. The Evolving Construct of Posttraumatic Stress Disorder (PTSD): DSM-5 Criteria Changes and Legal Implications

    PubMed Central

    Zoellner, Lori A.; Bedard-Gilligan, Michele A.; Jun, Janie J.; Marks, Libby H.; Garcia, Natalia M.

    2014-01-01

    In the DSM-5, the diagnosis of posttraumatic stress disorder (PTSD) has undergone multiple, albeit minor, changes. These changes include shifting PTSD placement from within the anxiety disorders into a new category of traumatic and stressor-related disorders, alterations in the definition of a traumatic event, shifting of the symptom cluster structure from three to four clusters, the addition of new symptoms including persistent negative beliefs and expectations about oneself or the world, persistent distorted blame of self or others, persistent negative trauma-related emotions, and risky or reckless behaviors, and the addition of a dissociative specifier. The evidence or lack thereof behind each of these changes is briefly reviewed. These changes, although not likely to change overall prevalence, have the potential to increase the heterogeneity of individuals receiving a PTSD diagnosis both by altering what qualifies as a traumatic event and by adding symptoms commonly occurring in other disorders such as depression, borderline personality disorder, and dissociative disorders. Legal implications of these changes include continued confusion regarding what constitutes a traumatic stressor, difficulties with differential diagnosis, increased ease in malingering, and improper linking of symptoms to causes of behavior. These PTSD changes are discussed within the broader context of DSM reliability and validity concerns. PMID:24470838

  8. [The altered topology of brain structural network in patients with acute stress response after traffic accident].

    PubMed

    Weng, Y F; Qi, R F; Zhang, X D; Zhang, L; Ke, J; Zhong, Y; Chen, F; Xu, Q; Lu, G M

    2017-09-19

    Objective: To explore the changes of brain activities in traffic accident survivors with acute stress response (ASR) within a week by using complex networks analysis method based on graph-theory, and to find out the alteration of topological properties in structural brain network. Method: From January, 2013 to February, 2016, twenty traffic accidents survivors with acute stress disorders (Acute Stress Disorder Interview, ASDI>3)and twenty healthy controls underwent the 3T diffusion tensor imaging (DTI) magnetic resonance imaging scan in Nanjing General Hospital.The graph-theory analysis method was used to compare the structural brain network properties and nodal features between ASR survivors and controls.Statistical analyses were also performed by including anxiety and depression as covariates to evaluate their effect.In additional, Pearson correlation was performed between abnormal parametric values and clinical indices. Results: (1) The brain structural networks had small-world properties in both groups; (2) while compared with healthy controls, patients with ASR showed increased weighted connectivity strength (Si, 1.36±0.47 vs 0.92±0.38, P=0.008) and nodal betweenness centrality (BCi, 20±15 vs 7±6, P=0.002) in left triangular part of inferior frontal (IFG triang_L), increased Si in orbital part of inferior frontal gyrus (1.10±0.31 vs 0.77±0.30, P=0.004) and obviously decreased Si in left caudate (0.75±0.24 vs 1.04±0.35, P=0.004); (3) furthermore, the inclusion of anxiety and depression as covariates abolished nodal parameters differences in IFG triang_L, left caudate, thalamus and inferior temporal gyrus. Conclusions: The brain structure network in ASR patients has small world properties.But nodal parameters change obviously in some nodes compared with healthy controls and mainly locate in prefrontal lobe and striatum. High levels of anxiety and depression in ASR patients may partly account for these alterations.

  9. Somatic reenactment in the treatment of posttraumatic stress disorder.

    PubMed

    Lindy, J D; Green, B L; Grace, M

    1992-01-01

    Somatic reenactments, like other intrusive symptoms in post-traumatic stress disorder, such as flashbacks and nightmares, reproduce the mental content of traumatic events. Four cases are presented from survivors of military trauma and civilian catastrophes. The patients were part of larger research projects carried out by the University of Cincinnati Traumatic Stress Study Center. Understanding such symptoms as repetitions of the trauma itself proved useful therapeutically, especially in consolidating the working alliance.

  10. Posttraumatic stress disorder among survivors of a kamikaze attack.

    PubMed

    Chara, P J; Chara, K A

    2001-12-01

    26 sailors who survived a Kamikaze attack during the battle for Okinawa in World War II were given two adapted forms of the Posttraumatic Stress Disorder Checklist-Civilian to assess the psychological reactions they had to the sinking of their ship. Depending on the assessment criteria used, their responses indicated significant stress reactions ranging from 8.3% to 44% of the sample. The findings provide evidence that a single combat experience can have lifelong, averse psychological effects.

  11. Circadian preferences, oxidative stress and inflammatory cytokines in bipolar disorder: A community study.

    PubMed

    Mondin, Thaise Campos; de Azevedo Cardoso, Taiane; Moreira, Fernanda Pedrotti; Wiener, Carolina; Oses, Jean Pierre; de Mattos Souza, Luciano Dias; Jansen, Karen; da Silva Magalhães, Pedro Vieira; Kapczinski, Flávio; da Silva, Ricardo Azevedo

    2016-12-15

    To assess circadian preference among a community sample of people with bipolar disorder, major depression and without any mood disorders. Secondly, we investigated the association of circadian preference with cytokines interleukin-6 (IL-6), interleukin-10 (IL-10) and, tumor necrosis factor alpha (TNF-α) and oxidative stress assessed by thiobarbituric acid reactive substances (TBARS), uric acid and Protein Carbonyl Content (PCC). A cross-sectional study nested in a population-based sample. Caseness was confirmed with the Structured Clinical Interview for DSM-IV. A sample of 215 participants, in whom we measured circadian preferences, IL-6, IL-10, TNF-α, TBARS, uric acid, PCC. Biological rhythms were evaluated using the Biological Interview of Assessment in Neuropsychiatry. Bipolar group presented a higher alteration in biological rhythms (40.40±9.78) when compared with the major depression group (36.35±9.18) and control group (27.61±6.89) p<0.001. Subjects with bipolar disorder who were active at night and had a day/night cycle reverse showed decreased levels of IL-6 (t, 44=2.096; p=0.042), (t, 44=2.213; p=0.032), respectively. In the bipolar disorder group subjects who presented day/night cycle reverse had lower TBARS levels (t, 41=2.612; p=0.013). TNF-α were decreased in subjects more active at night with bipolar disorder. Lower serum levels of IL-6, TNF-α and TBARS were associated with evening preference in bipolar disorder group. These findings suggest that chronotype may alter the levels of interleukins and oxidative stress levels in bipolar and healthy subjects. A better understanding of the role of circadian preferences in levels of interleukins and oxidative stress are needed. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. A review of acute stress disorder in DSM-5.

    PubMed

    Bryant, Richard A; Friedman, Matthew J; Spiegel, David; Ursano, Robert; Strain, James

    2011-09-01

    Acute stress disorder (ASD) was introduced into DSM-IV to describe acute stress reactions (ASRs) that occur in the initial month after exposure to a traumatic event and before the possibility of diagnosing posttraumatic stress disorder (PTSD), and to identify trauma survivors in the acute phase who are high risk for PTSD. This review considers ASD in relation to other diagnostic approaches to acute stress responses, critiques the evidence of the predictive power of ASD, and discusses ASD in relation to Adjustment Disorder. The evidence suggests that ASD does not adequately identify most people who develop PTSD. This review presents a number of options and preliminary considerations to be considered for DSM-5. It is proposed that ASD be limited to describing severe ASRs (that are not necessarily precursors of PTSD). The evidence suggests that the current emphasis on dissociation may be overly restrictive and does not recognize the heterogeneity of early posttraumatic stress responses. It is proposed that ASD may be better conceptualized as the severity of acute stress responses that does not require specific clusters to be present.

  13. Chronic stress induces structural alterations in splenic lymphoid tissue that are associated with changes in corticosterone levels in wistar-kyoto rats.

    PubMed

    Hernandez, María Eugenia; Martinez-Mota, Lucia; Salinas, Citlaltepetl; Marquez-Velasco, Ricardo; Hernandez-Chan, Nancy G; Morales-Montor, Jorge; Pérez-Tapia, Mayra; Streber, María L; Granados-Camacho, Ivonne; Becerril, Enrique; Javier, Baquera-Heredia; Pavón, Lenin

    2013-01-01

    Major depressive disorder patients present chronic stress and decreased immunity. The Wistar-Kyoto rat (WKY) is a strain in which the hypothalamic-pituitary-adrenal axis is overactivated. To determine whether chronic stress induces changes in corticosterone levels and splenic lymphoid tissue, 9-week-old male rats were subject to restraint stress (3 h daily), chemical stress (hydrocortisone treatment, 50 mg/Kg weight), mixed stress (restraint plus hydrocortisone), or control treatment (without stress) for 1, 4, and 7 weeks. The serum corticosterone levels by RIA and spleens morphology were analyzed. Corticosterone levels as did the structure, size of the follicles and morphology of the parenchyma (increase in red pulp) in the spleen, varied depending on time and type of stressor. These changes indicate that chronic stress alters the immune response in the spleen in WKY rats by inducing morphological changes, explaining in part the impaired immunity that develops in organisms that are exposed to chronic stress.

  14. Post-traumatic stress disorder: theory and treatment update.

    PubMed

    Kirkpatrick, Heather A; Heller, Grant M

    2014-01-01

    Post-traumatic stress disorder (PTSD) is one of the few mental disorders in which the cause is readily identifiable. In this article, we review the new Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria, prevalence, and presentation of patients with PTSD in primary care. The purpose of this article is to review current literature regarding theory, etiology, and treatment effectiveness. Key findings in terms of neurobiological underpinnings with implications for future treatment are discussed. Recommendations regarding effective psychotherapy and pharmacotherapy, emerging treatment, and management issues in primary care settings are offered.

  15. Measuring secondary traumatic stress symptoms in military spouses with the posttraumatic stress disorder checklist military version.

    PubMed

    Bjornestad, Andrea G; Schweinle, Amy; Elhai, Jon D

    2014-12-01

    Little research to date has examined secondary traumatic stress symptoms in spouses of military veterans. This study investigated the presence and severity of posttraumatic stress symptoms in a sample of 227 Army National Guard veterans and secondary traumatic stress symptoms among their spouses. The veterans completed the posttraumatic stress disorder (PTSD) Checklist Military Version (PCL-M) (Weathers et al., 1993) to determine the probable prevalence rate of posttraumatic stress symptoms. A modified version of the PCL-M was used to assess secondary traumatic stress symptoms in the spouses. A confirmatory factor analysis showed that the modified version of the PCL-M used to assess secondary traumatic stress symptoms in spouses fits using the same four-factor PTSD structure as the PCL-M for veterans. This study provides initial evidence on the underlying symptom structure of secondary traumatic stress symptoms among spouses of traumatic event victims.

  16. Alterations to oxidative stress markers in dogs after a short-term stress during transport.

    PubMed

    Ferreira, Chayanne S; Vasconcellos, Ricardo S; Pedreira, Raquel S; Silva, Flavio L; Sá, Fabiano C; Kroll, Fernanda S A; Maria, Ana P J; Venturini, Katiani S; Carciofi, Aulus C

    2014-01-01

    While methods to evaluate antioxidant capacity in animals exist, one problem with the models is induction of oxidative stress. It is necessary to promote a great enough challenge to induce measurable alterations to oxidative parameters while ensuring the protocol is compatible with animal welfare. The aim of the present study was to evaluate caged transport as a viable short-term stress that would significantly affect oxidative parameters. Twenty adult Beagle dogs, maintained on the same diet for 60 d prior to the transport, were included in the study. To simulate the stress, the dogs were housed in pairs in transport cages (1·0 m × 1·0 m × 1·5 m), placed on a truck coupled to a trailer and transported for a period of 15 min. Blood collection was performed immediately before and again 3 h after the transportation to evaluate oxidative parameters in blood serum, including thiobarbituric acid reactive substances (TBARS), total antioxidant capacity (TAC), sequestration activity of the radical 2,2-diphenyl-1-picryl-hydrazyl (DPPH•), protein carbonylation (PC), total sulfhydryl groups (SH), alpha-tocopherol (αToc) and retinol (Ret). PC, SH and αToc were not significantly changed in the study; however, TBARS, TAC and DPPH increased, whereas Ret decreased after the transport. Although the lack of a control group of dogs not submitted to transport is a limitation to be considered, we conclude that the transport model is effective in inducing an antioxidant response in dogs and relevant blood parameters show sensitivity to this proposed model.

  17. Prenatal stress alters the behavior and dendritic morphology of the medial orbitofrontal cortex in mouse offspring during lactation.

    PubMed

    Gutiérrez-Rojas, Cristian; Pascual, Rodrigo; Bustamante, Carlos

    2013-11-01

    Several preclinical and clinical studies have shown that prenatal stress alters neuronal dendritic development in the prefrontal cortex, together with behavioral disturbances (anxiety). Nevertheless, neither whether these alterations are present during the lactation period, nor whether such findings may reflect the onset of anxiety disorders observed in childhood and adulthood has been studied. The central aim of the present study was to determine the effects of prenatal stress on the neuronal development and behavior of mice offspring during lactation (postnatal days 14 and 21). We studied 24 CF-1 male mice, grouped as follows: (i) control P14 (n=6), (ii) stressed P14 (n=6), (iii) control P21 (n=6) and (iv) stressed P21 (n=6). On the corresponding days, animals were evaluated with the open field test and sacrificed. Their brains were then stained in Golgi-Cox solution for 30 days. The morphological analysis dealt with the study of 96 pyramidal neurons. The results showed, first, that prenatal stress resulted in a significant (i) decrease in the apical dendritic length of pyramidal neurons in the orbitofrontal cortex at postnatal day 14, (ii) increase in the apical dendritic length of pyramidal neurons in the orbitofrontal cortex at postnatal day 21, and (iii) reduction in exploratory behavior at postnatal day 14 and 21.

  18. Ripening, storage temperature, ethylene action, and oxidative stress alter apple peel phytosterol metabolism.

    PubMed

    Rudell, David R; Buchanan, David A; Leisso, Rachel S; Whitaker, Bruce D; Mattheis, James P; Zhu, Yanmin; Varanasi, Vijay

    2011-08-01

    The chilling conditions of apple cold storage can provoke an economically significant necrotic peel disorder called superficial scald (scald) in susceptible cultivars. Disorder development can be reduced by inhibiting ethylene action or oxidative stress as well as intermittent warming. It was previously demonstrated that scald is preceded by a metabolomic shift that results in altered levels of various classes of triterpenoids, including metabolites with mass spectral features similar to β-sitosterol. In this study, a key class of phytosterol metabolites was identified. Changes in peel tissue levels of conjugates of β-sitosterol and campesterol, including acylated steryl glycosides (ASG), steryl glycosides (SG) and steryl esters (SE), as well as free sterols (FS), were determined during the period of scald development. Responses to pre-storage treatment with the ethylene action inhibitor, 1-methylcyclopropene, or an antioxidant (diphenylamine), rapid temperature elevation, and cold acclimation using intermittent warming treatments were evaluated. Diphenylamine, 1-MCP, and intermittent warming all reduced or prevented scald development. ASG levels increased and SE levels decreased in untreated control fruit during storage. Removing fruit from cold storage to ambient temperature induced rapid shifts in ASG and SE fatty acyl moieties from unsaturated to saturated. FS and SG levels remained relatively stable during storage but SG levels increased following a temperature increase after storage. ASG, SE, and SG levels did not increase during 6 months cold storage in fruit subjected to intermittent warming treatment. Overall, the results show that apple peel phytosteryl conjugate metabolism is influenced by storage duration, oxidative stress, ethylene action/ripening, and storage temperature.

  19. Health functioning impairments associated with posttraumatic stress disorder, anxiety disorders, and depression.

    PubMed

    Zayfert, Claudia; Dums, Aricca R; Ferguson, Robert J; Hegel, Mark T

    2002-04-01

    Although anxiety disorders have been associated with impairments in self-reported health functioning, the relative effect of various anxiety disorders has not been studied. We compared health functioning of patients with a principal diagnosis of posttraumatic stress disorder (PTSD), panic disorder (PD), generalized anxiety disorder (GAD), and major depressive disorder (MDD). Patients with PTSD and MDD were equally impaired on overall mental health functioning, and both were significantly worse than patients with PD and GAD. PTSD was associated with significantly worse physical health functioning relative to PD, GAD, and MDD. Hierarchical regression showed that the association of PTSD with physical health functioning was unique and was not caused by the effects of age, depression, or comorbid anxiety disorders. Both PTSD and comorbid anxiety accounted for unique variance in mental functioning. These results highlight the association of PTSD with impaired physical and mental functioning and suggest that effective treatment of PTSD may affect overall health.

  20. Acute and Chronic Plasma Metabolomic and Liver Transcriptomic Stress Effects in a Mouse Model with Features of Post-Traumatic Stress Disorder

    PubMed Central

    Gautam, Aarti; D’Arpa, Peter; Donohue, Duncan E.; Muhie, Seid; Chakraborty, Nabarun; Luke, Brian T.; Grapov, Dmitry; Carroll, Erica E.; Meyerhoff, James L.; Hammamieh, Rasha; Jett, Marti

    2015-01-01

    Acute responses to intense stressors can give rise to post-traumatic stress disorder (PTSD). PTSD diagnostic criteria include trauma exposure history and self-reported symptoms. Individuals who meet PTSD diagnostic criteria often meet criteria for additional psychiatric diagnoses. Biomarkers promise to contribute to reliable phenotypes of PTSD and comorbidities by linking biological system alterations to behavioral symptoms. Here we have analyzed unbiased plasma metabolomics and other stress effects in a mouse model with behavioral features of PTSD. In this model, C57BL/6 mice are repeatedly exposed to a trained aggressor mouse (albino SJL) using a modified, resident-intruder, social defeat paradigm. Our recent studies using this model found that aggressor-exposed mice exhibited acute stress effects including changed behaviors, body weight gain, increased body temperature, as well as inflammatory and fibrotic histopathologies and transcriptomic changes of heart tissue. Some of these acute stress effects persisted, reminiscent of PTSD. Here we report elevated proteins in plasma that function in inflammation and responses to oxidative stress and damaged tissue at 24 hrs post-stressor. Additionally at this acute time point, transcriptomic analysis indicated liver inflammation. The unbiased metabolomics analysis showed altered metabolites in plasma at 24 hrs that only partially normalized toward control levels after stress-withdrawal for 1.5 or 4 wks. In particular, gut-derived metabolites were altered at 24 hrs post-stressor and remained altered up to 4 wks after stress-withdrawal. Also at the 4 wk time point, hyperlipidemia and suppressed metabolites of amino acids and carbohydrates in plasma coincided with transcriptomic indicators of altered liver metabolism (activated xenobiotic and lipid metabolism). Collectively, these system-wide sequelae to repeated intense stress suggest that the simultaneous perturbed functioning of multiple organ systems (e.g., brain, heart

  1. Acute and chronic plasma metabolomic and liver transcriptomic stress effects in a mouse model with features of post-traumatic stress disorder.

    PubMed

    Gautam, Aarti; D'Arpa, Peter; Donohue, Duncan E; Muhie, Seid; Chakraborty, Nabarun; Luke, Brian T; Grapov, Dmitry; Carroll, Erica E; Meyerhoff, James L; Hammamieh, Rasha; Jett, Marti

    2015-01-01

    Acute responses to intense stressors can give rise to post-traumatic stress disorder (PTSD). PTSD diagnostic criteria include trauma exposure history and self-reported symptoms. Individuals who meet PTSD diagnostic criteria often meet criteria for additional psychiatric diagnoses. Biomarkers promise to contribute to reliable phenotypes of PTSD and comorbidities by linking biological system alterations to behavioral symptoms. Here we have analyzed unbiased plasma metabolomics and other stress effects in a mouse model with behavioral features of PTSD. In this model, C57BL/6 mice are repeatedly exposed to a trained aggressor mouse (albino SJL) using a modified, resident-intruder, social defeat paradigm. Our recent studies using this model found that aggressor-exposed mice exhibited acute stress effects including changed behaviors, body weight gain, increased body temperature, as well as inflammatory and fibrotic histopathologies and transcriptomic changes of heart tissue. Some of these acute stress effects persisted, reminiscent of PTSD. Here we report elevated proteins in plasma that function in inflammation and responses to oxidative stress and damaged tissue at 24 hrs post-stressor. Additionally at this acute time point, transcriptomic analysis indicated liver inflammation. The unbiased metabolomics analysis showed altered metabolites in plasma at 24 hrs that only partially normalized toward control levels after stress-withdrawal for 1.5 or 4 wks. In particular, gut-derived metabolites were altered at 24 hrs post-stressor and remained altered up to 4 wks after stress-withdrawal. Also at the 4 wk time point, hyperlipidemia and suppressed metabolites of amino acids and carbohydrates in plasma coincided with transcriptomic indicators of altered liver metabolism (activated xenobiotic and lipid metabolism). Collectively, these system-wide sequelae to repeated intense stress suggest that the simultaneous perturbed functioning of multiple organ systems (e.g., brain, heart

  2. Ankyrin-3 as a molecular marker of early-life stress and vulnerability to psychiatric disorders.

    PubMed

    Luoni, A; Massart, R; Nieratschker, V; Nemoda, Z; Blasi, G; Gilles, M; Witt, S H; Suderman, M J; Suomi, S J; Porcelli, A; Rizzo, G; Fazio, L; Torretta, S; Rampino, A; Berry, A; Gass, P; Cirulli, F; Rietschel, M; Bertolino, A; Deuschle, M; Szyf, M; Riva, M A

    2016-11-08

    Exposure to early-life stress (ELS) may heighten the risk for psychopathology at adulthood. Here, in order to identify common genes that may keep the memory of ELS through changes in their methylation status, we intersected methylome analyses performed in different tissues and time points in rats, non-human primates and humans, all characterized by ELS. We identified Ankyrin-3 (Ank3), a scaffolding protein with a strong genetic association for psychiatric disorders, as a gene persistently affected by stress exposure. In rats, Ank3 methylation and mRNA changes displayed a specific temporal profile during the postnatal development. Moreover, exposure to prenatal stress altered the interaction of ankyrin-G, the protein encoded by Ank3 enriched in the post-synaptic compartment, with PSD95. Notably, to model in humans a gene by early stress interplay on brain phenotypes during cognitive performance, we demonstrated an interaction between functional variation in Ank3 gene and obstetric complications on working memory in healthy adult subjects. Our data suggest that alterations of Ank3 expression and function may contribute to the effects of ELS on the development of psychiatric disorders.

  3. Ankyrin-3 as a molecular marker of early-life stress and vulnerability to psychiatric disorders

    PubMed Central

    Luoni, A; Massart, R; Nieratschker, V; Nemoda, Z; Blasi, G; Gilles, M; Witt, S H; Suderman, M J; Suomi, S J; Porcelli, A; Rizzo, G; Fazio, L; Torretta, S; Rampino, A; Berry, A; Gass, P; Cirulli, F; Rietschel, M; Bertolino, A; Deuschle, M; Szyf, M; Riva, M A

    2016-01-01

    Exposure to early-life stress (ELS) may heighten the risk for psychopathology at adulthood. Here, in order to identify common genes that may keep the memory of ELS through changes in their methylation status, we intersected methylome analyses performed in different tissues and time points in rats, non-human primates and humans, all characterized by ELS. We identified Ankyrin-3 (Ank3), a scaffolding protein with a strong genetic association for psychiatric disorders, as a gene persistently affected by stress exposure. In rats, Ank3 methylation and mRNA changes displayed a specific temporal profile during the postnatal development. Moreover, exposure to prenatal stress altered the interaction of ankyrin-G, the protein encoded by Ank3 enriched in the post-synaptic compartment, with PSD95. Notably, to model in humans a gene by early stress interplay on brain phenotypes during cognitive performance, we demonstrated an interaction between functional variation in Ank3 gene and obstetric complications on working memory in healthy adult subjects. Our data suggest that alterations of Ank3 expression and function may contribute to the effects of ELS on the development of psychiatric disorders. PMID:27824361

  4. Keratins Are Altered in Intestinal Disease-Related Stress Responses

    PubMed Central

    Helenius, Terhi O.; Antman, Cecilia A.; Asghar, Muhammad Nadeem; Nyström, Joel H.; Toivola, Diana M.

    2016-01-01

    Keratin (K) intermediate filaments can be divided into type I/type II proteins, which form obligate heteropolymers. Epithelial cells express type I-type II keratin pairs, and K7, K8 (type II) and K18, K19 and K20 (type I) are the primary keratins found in the single-layered intestinal epithelium. Keratins are upregulated during stress in liver, pancreas, lung, kidney and skin, however, little is known about their dynamics in the intestinal stress response. Here, keratin mRNA, protein and phosphorylation levels were studied in response to murine colonic stresses modeling human conditions, and in colorectal cancer HT29 cells. Dextran sulphate sodium (DSS)-colitis was used as a model for intestinal inflammatory stress, which elicited a strong upregulation and widened crypt distribution of K7 and K20. K8 levels were slightly downregulated in acute DSS, while stress-responsive K8 serine-74 phosphorylation (K8 pS74) was increased. By eliminating colonic microflora using antibiotics, K8 pS74 in proliferating cells was significantly increased, together with an upregulation of K8 and K19. In the aging mouse colon, most colonic keratins were upregulated. In vitro, K8, K19 and K8 pS74 levels were increased in response to lipopolysaccharide (LPS)-induced inflammation in HT29 cells. In conclusion, intestinal keratins are differentially and dynamically upregulated and post-translationally modified during stress and recovery. PMID:27626448

  5. Perceived Control Alters the Effect of Acute Stress on Persistence

    PubMed Central

    Bhanji, Jamil P.; Kim, Eunbin S.; Delgado, Mauricio R.

    2015-01-01

    We often encounter setbacks while pursuing our goals. Success requires that we cope with these negative outcomes and choose to persist in spite of them. For example, learners may be more likely to continue a course after failing an assessment if they control their emotional reactions to the setback and study harder. However, the ability to effectively cope with the negative emotion inherent in such setbacks can be compromised by acute stress present in daily life (e.g., struggles in the household), which can subsequently lead to problems with persisting with a goal. The present study examined whether increasing the perception of control over setbacks (e.g., belief that a setback was caused by a correctable mistake rather than uncontrollable factors) can guard against the influence of a prior acute stressor on reactions to setbacks. Participants underwent a socially-evaluated cold water stress or a non-stress control procedure. Afterwards, they performed a behavioral task designed to measure persistence through controllable and uncontrollable setbacks. We observed that exposure to an acute stressor led to a detrimental effect on decision making by decreasing persistence behavior. Importantly, we also observed that the perception of control protected against the effect of preexisting stress and helped promote persistence. That is, stress impaired persistence through uncontrollable setbacks, but the impairment was alleviated by presenting setbacks as controllable. The findings demonstrate a potential avenue for improving the maintenance of goals aimed at behavior change, which can be susceptible to effects of stress. PMID:26726915

  6. Stress induces altered CRE/CREB pathway activity and BDNF expression in the hippocampus of glucocorticoid receptor-impaired mice.

    PubMed

    Alboni, Silvia; Tascedda, Fabio; Corsini, Daniela; Benatti, Cristina; Caggia, Federica; Capone, Giacomo; Barden, Nicholas; Blom, Joan M C; Brunello, Nicoletta

    2011-06-01

    The gene coding for the neurotrophin Brain-Derived Neurotrophic Factor (BDNF) is a stress-responsive gene. Changes in its expression may underlie some of the pathological effects of stress-related disorders like depression. Data on the stress-induced regulation of the expression of BDNF in pathological conditions are rare because often research is conducted using healthy animals. In our experiments, we used transgenic mice with glucocorticoid receptor impaired (GR-i) expression in the hypothalamus created as a tool to study the neuroendocrine changes occurring in stress-related disorders. First, under basal condition, GR-i mice displayed lower levels of BDNF exons IX and IV and decreased CRE(BDNF) binding activity with respect to wild-type (WT) mice in the hippocampus. Then, we exposed GR-i and WT mice to an acute restraint stress (ARS) to test the hypothesis that GR-i mice display: 1] different ARS induced expression of BDNF, and 2] altered activation of signaling pathways implicated in regulating BDNF gene expression in the hippocampus with respect to WT mice. Results indicate that ARS enhanced BDNF mRNA expression mainly in the CA3 hippocampal sub-region of GR-i mice in the presence of enhanced levels of pro-BDNF protein, while no effect was observed in WT mice. Moreover, ARS reduced CREB signaling and binding to the BDNF promoter in GR-i mice but enhanced signaling and binding, possibly through ERK1/2 activation, in WT mice. Thus, life-long central GR dysfunction resulted in an altered sensitivity at the transcriptional level that may underlie an impaired response to an acute psycho-physical stress. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'.

  7. Differential melatonin alterations in cerebrospinal fluid and serum of patients with major depressive disorder and bipolar disorder.

    PubMed

    Bumb, J M; Enning, F; Mueller, J K; van der List, Till; Rohleder, C; Findeisen, P; Noelte, I; Schwarz, E; Leweke, F M

    2016-07-01

    Melatonin, which plays an important role for regulation of circadian rhythms and the sleep/wake cycle has been linked to the pathophysiology of major depressive and bipolar disorder. Here we investigated melatonin levels in cerebrospinal fluid (CSF) and serum of depression and bipolar patients to elucidate potential differences and commonalities in melatonin alterations across the two disorders. Using enzyme-linked immunosorbent assays, CSF and serum melatonin levels were measured in 108 subjects (27 healthy volunteers, 44 depressed and 37 bipolar patients). Covariate adjusted multiple regression analysis was used to investigate group differences in melatonin levels. In CSF, melatonin levels were significantly decreased in bipolar (P<0.001), but not major depressive disorder. In serum, we observed a significant melatonin decrease in major depressive (P=0.003), but not bipolar disorder. No associations were found between serum and CSF melatonin levels or between melatonin and measures of symptom severity or sleep disruptions in either condition. This study suggests the presence of differential, body fluid specific alterations of melatonin levels in bipolar and major depressive disorder. Further, longitudinal studies are required to explore the disease phase dependency of melatonin alterations and to mechanistically explore the causes and consequences of site-specific alterations. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Protective effect of alprazolam in acute immobilization stress-induced certain behavioral and biochemical alterations in mice.

    PubMed

    Goyal, Richa; Anil, Kumar

    2007-01-01

    Stress can be viewed as a cause of adverse circumstance that induces a wide range of biochemical and behavioral changes. Oxidative stress is a major contributor to the genesis of neurodegenerative and neuropsychiatric problems. In the present study, we investigated the protective effect of alprazolam in acute immobilization-induced various behavioral and biochemical alteration in mice. Mice were immobilized for a period of 6 h. Alprazolam (0.25 and 0.5 mg/kg, i.p.) was administered 30 min before subjecting the animals to acute stress and several behavioral (mirror chamber, actophotometer, tail flick test) and biochemical tests (malondialdehyde level, glutathione, catalase, nitrite and protein) were performed. Acute immobilization stress for a period of 6 h caused severe anxiety, analgesia and decreased locomotor activity in mice. Biochemical analyses revealed an increase in malondialdehyde, nitrite level and depleted glutathione and catalase activity in stressed brain. Pretreatment with alprazolam (0.25 and 0.5 mg/kg, i.p.) significantly reversed immobilization stress-induced anxiety, analgesia and impaired locomotor activity. Biochemically, alprazolam pretreatment decreased malondialdehyde, nitrite activity and restored reduced glutathione level and catalase activity. These results suggest that alprazolam has a neuroprotective effect and can be used in the treatment and management of stress and related disorders.

  9. Improved growth and stress tolerance in the Arabidopsis oxt1 mutant triggered by altered adenine metabolism.

    PubMed

    Sukrong, Suchada; Yun, Kil-Young; Stadler, Patrizia; Kumar, Charan; Facciuolo, Tony; Moffatt, Barbara A; Falcone, Deane L

    2012-11-01

    Plants perceive and respond to environmental stresses with complex mechanisms that are often associated with the activation of antioxidant defenses. A genetic screen aimed at isolating oxidative stress-tolerant lines of Arabidopsis thaliana has identified oxt1, a line that exhibits improved tolerance to oxidative stress and elevated temperature but displays no apparent deleterious growth effects under non-stress conditions. Oxt1 harbors a mutation that arises from the altered expression of a gene encoding adenine phosphoribosyltransferase (APT1), an enzyme that converts adenine to adenosine monophosphate (AMP), indicating a link between purine metabolism, whole-plant growth responses, and stress acclimation. The oxt1 mutation results in decreased APT1 expression that leads to reduced enzymatic activity. Correspondingly, oxt1 plants possess elevated levels of adenine. Decreased APT enzyme activity directly correlates with stress resistance in transgenic lines that ectopically express APT1. The metabolic alteration in oxt1 plants also alters the expression of several antioxidant defense genes and the response of these genes to oxidative challenge. Finally, it is shown that manipulation of adenine levels can induce stress tolerance to wild-type plants. Collectively, these results show that alterations in cellular adenine levels can trigger stress tolerance and improve growth, leading to increases in plant biomass. The results also suggest that adenine might play a part in the signals that modulate responses to abiotic stress and plant growth.

  10. Combat posttraumatic stress disorder, substance use disorders, and traumatic brain injury.

    PubMed

    Brady, Kathleen T; Tuerk, Peter; Back, Sudie E; Saladin, Michael E; Waldrop, Angela E; Myrick, Hugh

    2009-12-01

    Among both civilian and veteran populations, substance use disorders (SUDs) and anxiety disorders frequently co-occur. One of the most common comorbid anxiety disorder is posttraumatic stress disorder (PTSD), a condition which may develop after exposure to traumatic events, such as military combat. In comparison with the general population, rates of both SUDs and PTSD are elevated among veterans. Recent data show that soldiers returning from Iraq and Afghanistan demonstrate high rates of co-occurring SUDs, PTSD, and traumatic brain injury. Careful assessment of these conditions is critical and may be complicated by symptom overlap. More research targeting integrated interventions for these conditions is needed to establish optimal treatments.

  11. The Psychophysiology of Posttraumatic Stress Disorder: A Meta-Analysis

    ERIC Educational Resources Information Center

    Pole, Nnamdi

    2007-01-01

    This meta-analysis of 58 resting baseline studies, 25 startle studies, 17 standardized trauma cue studies, and 22 idiographic trauma cue studies compared adults with and without posttraumatic stress disorder (PTSD) on psychophysiological variables: facial electromyography (EMG), heart rate (HR), skin conductance (SC), and blood pressure.…

  12. Acute Stress Disorder: Conceptual Issues and Treatment Outcomes

    ERIC Educational Resources Information Center

    Koucky, Ellen M.; Galovski, Tara E.; Nixon, Reginald D. V.

    2012-01-01

    Acute stress disorder (ASD) was included as a diagnosis to the 4th edition of the "Diagnostic and Statistical Manual" (American Psychiatric Association, 1994) as a way of describing pathological reactions in the first month following a trauma. Since that time, ASD has been the focus of some controversy, particularly regarding the theoretical basis…

  13. Posttraumatic Stress Disorder in Children: What Elementary Teachers Should Know

    ERIC Educational Resources Information Center

    Ray, Jan

    2014-01-01

    Posttraumatic stress disorder (PTSD) is not limited to the men and women who have been exposed to the horrors of war through military service. Children who are exposed to traumatic and life-threatening events, such as school shootings, physical and sexual abuse, and community violence, also can suffer from PTSD. This article explores the causes,…

  14. Narrative Therapy to Prevent Illness-Related Stress Disorder

    ERIC Educational Resources Information Center

    Petersen, Suni; Bull, Carolyn; Propst, Olivia; Dettinger, Sara; Detwiler, Laura

    2005-01-01

    More than 94% of cancer patients described the experience as the most traumatic event they have ever faced and 13% have posttraumatic stress disorder (PTSD) in the aftermath. Empirical evidence demonstrates that certain behaviors lead to more positive health outcomes. Although many patients automatically engage in these behaviors, many others do…

  15. Posttraumatic Stress Disorder in Children: What Elementary Teachers Should Know

    ERIC Educational Resources Information Center

    Ray, Jan

    2014-01-01

    Posttraumatic stress disorder (PTSD) is not limited to the men and women who have been exposed to the horrors of war through military service. Children who are exposed to traumatic and life-threatening events, such as school shootings, physical and sexual abuse, and community violence, also can suffer from PTSD. This article explores the causes,…

  16. The use of clonidine in post-traumatic stress disorder.

    PubMed

    Porter, D M; Bell, C C

    1999-08-01

    This case report examines the use of clonidine to successfully treat a child suffering from post-traumatic stress disorder (PTSD). This case shows an unintentional washout period that exemplifies a cause-effect relationship between clonidine and the inhibition of reenactment symptoms of PTSD.

  17. 75 FR 41092 - Stressor Determinations for Posttraumatic Stress Disorder

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-15

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF VETERANS AFFAIRS 38 CFR Part 3 RIN 2900-AN32 Stressor Determinations for Posttraumatic Stress Disorder Correction In rule document 2010-16885 beginning on page 39843 in the issue of Tuesday, July 13, 2010 make...

  18. Dissociative symptoms in posttraumatic stress disorder: diagnosis and treatment.

    PubMed

    Steiner, Hans; Carrion, Victor; Plattner, Belinda; Koopman, Cheryl

    2003-04-01

    This article explores the complex relationship between dissociation and psychiatric trauma. Dissociation is described as a defense reaction, a risk factor for the development of posttraumatic stress disorder, and as a set of syndromal disturbances. The authors discuss various models proposed for the relationship between these. They outline developmental considerations in diagnosis and treatment and end by discussing further needed research.

  19. Being a Wife of a Veteran with Posttraumatic Stress Disorder

    ERIC Educational Resources Information Center

    Dekel, Rachel; Goldblatt, Hadass; Keidar, Michal; Solomon, Zahava; Polliack, Michael

    2005-01-01

    We present the findings from a qualitative study examining the marital perceptions of 9 wives of veterans with posttraumatic stress disorder (PTSD). Data were from a semistructured in-depth focus group interview. Findings reveal how the lives of these women largely revolved around their husbands' illness. The wives faced constant tension between…

  20. Preclinical Perspectives on Posttraumatic Stress Disorder Criteria in DSM-5

    PubMed Central

    Tye, Susannah; Van Voorhees, Elizabeth; Hu, Chunling; Lineberry, Timothy

    2015-01-01

    Posttraumatic stress disorder (PTSD) now sits within the newly created “Trauma- and Stressor-Related Disorders” section of the Diagnostic and Statistical Manual of Mental Disorders (fifth edition; DSM-5). Through the refinement and expansion of diagnostic criteria, the DSM-5 version better clarifies the broad and pervasive effects of trauma on functioning, as well as the impact of development on trauma reactions. Aggressive and dissociative symptoms are more thoroughly characterized, reflecting increasing evidence that reactions to trauma often reach beyond the domains of fear and anxiety (these latter domains were emphasized in DSM-IV). These revised criteria are supported by decades of preclinical and clinical research quantifying traumatic stress–induced changes in neurobiological and behavioral function. Several features of the DSM-5 PTSD criteria are similarly and consistently represented in preclinical animal models and humans following exposure to extreme stress. In rodent models, for example, increases in anxiety-like, helplessness, or aggressive behavior, along with disruptions in circadian/neurovegetative function, are typically induced by severe, inescapable, and uncontrollable stress. These abnormalities are prominent features of PTSD and can help us in understanding the pathophysiology of this and other stress-associated psychiatric disorders. In this article we examine some of the changes to the diagnostic criteria of PTSD in the context of trauma-related neurobiological dysfunction, and discuss implications for how preclinical data can be useful in current and future clinical conceptualizations of trauma and trauma-related psychiatric disorders. PMID:25563569

  1. Assessment of Posttraumatic Stress Disorder in World War II Veterans.

    ERIC Educational Resources Information Center

    Engdahl, Brian E.; And Others

    1996-01-01

    Four posttraumatic stress disorder (PTSD) scales were compared in a community sample of 330 former prisoners of war and World War II combat veterans. The Mississippi Scale for Combat-Related PTSD, the Minnesota Multiphasic Personality Inventory-2, and the Impact of Event Scale demonstrated moderate relationships with PTSD. (SLD)

  2. Penn Inventory for Posttraumatic Stress Disorder: Psychometric Properties.

    ERIC Educational Resources Information Center

    Hammarberg, Melvyn

    1992-01-01

    A three-phase study was conducted to develop and validate the Penn Inventory for Posttraumatic Stress Disorder (PTSD), a 26-item self-report measure. Results with 83 and 98 combat veterans and with 76 general population patients and disaster survivors support usefulness of the measure. (SLD)

  3. The Psychophysiology of Posttraumatic Stress Disorder: A Meta-Analysis

    ERIC Educational Resources Information Center

    Pole, Nnamdi

    2007-01-01

    This meta-analysis of 58 resting baseline studies, 25 startle studies, 17 standardized trauma cue studies, and 22 idiographic trauma cue studies compared adults with and without posttraumatic stress disorder (PTSD) on psychophysiological variables: facial electromyography (EMG), heart rate (HR), skin conductance (SC), and blood pressure.…

  4. Trauma Exposure and Posttraumatic Stress Disorder in Delinquent Female Adolescents

    ERIC Educational Resources Information Center

    Ariga, Michio; Uehara, Toru; Takeuchi, Kazuo; Ishige, Yoko; Nakano, Reiko; Mikuni, Masahiko

    2008-01-01

    Background: Although juveniles within the justice system have high psychiatric morbidity, few comprehensive investigations have shown posttraumatic stress disorder (PTSD) in female delinquents. Here, we aim to describe the nature and extent of PTSD and trauma exposure and to clarify the relationships among comorbidity and psychosocial factors in…

  5. Posttraumatic Stress Disorder and Sexual Assault in Women

    ERIC Educational Resources Information Center

    Klump, Meredith C.

    2006-01-01

    This paper presents a review of the research literature on the factors associated with the development of posttraumatic stress disorder (PTSD) in women victims of rape and sexual assault. Various studies have linked preassault variables (such as childhood abuse), and assault variables (including injury and perceived life threat during the assault)…

  6. Trauma Exposure and Posttraumatic Stress Disorder in Delinquent Female Adolescents

    ERIC Educational Resources Information Center

    Ariga, Michio; Uehara, Toru; Takeuchi, Kazuo; Ishige, Yoko; Nakano, Reiko; Mikuni, Masahiko

    2008-01-01

    Background: Although juveniles within the justice system have high psychiatric morbidity, few comprehensive investigations have shown posttraumatic stress disorder (PTSD) in female delinquents. Here, we aim to describe the nature and extent of PTSD and trauma exposure and to clarify the relationships among comorbidity and psychosocial factors in…

  7. In Vitro Flooding of a Childhood Posttraumatic Stress Disorder.

    ERIC Educational Resources Information Center

    Saigh, Philip A.

    1987-01-01

    An in vitro flooding package was used to treat the posttraumatic stress disorder of a 10-year-old girl. Traumatic scenes were identified and stimulus and response imagery cues were presented according to a multiple baseline across traumatic scenes design. Postreatment and follow-up assessment revealed the positive influence of the treatment.…

  8. The changing face of posttraumatic stress disorder in modern warfare.

    PubMed

    Wallace, Duncan; Heffernan, Kristi

    2017-08-01

    This study examined aspects of modern warfare and determined whether they have changed the clinical presentation of posttraumatic stress disorder (PTSD). The relationship between PTSD, mild traumatic brain injury, unmanned aerial vehicle operations and women in combat examined. It was concluded that there are significant changes in how contemporary combat veterans may present with PTSD.

  9. Posttraumatic stress disorder: shifting toward a developmental framework.

    PubMed

    Carrion, Victor G; Kletter, Hilit

    2012-07-01

    This article reviews the current classification of posttraumatic stress disorder and its limitations when applied to youth. Distinctions are made between single-event and multiple-event traumas. Diagnosis, neurobiology, treatment development, and treatment outcomes are presented. A summary of current empirical interventions is provided. The authors present implications for future research and for clinical practice.

  10. Connection and Recovery: Posttraumatic Stress Disorder and School Reintegration.

    ERIC Educational Resources Information Center

    Cook-Cottone, Catherine

    This paper provides an introduction to Posttraumatic Stress Disorder (PTSD) in a manner that facilitates the interested learner's further exploration. It presents theoretical references and reviews the social factors and epidemiology of PTSD in children and adolescents. The psychobiology of PTSD is described in relation to the types of memory it…

  11. [Simple and complex post-traumatic stress disorders. Diagnostic and therapeutic approaches].

    PubMed

    Roestel, C; Kersting, A

    2008-07-01

    The prevalence rates of post-traumatic stress disorders are high in the general population (5-10%). The main diagnostic criteria include the experience of an event of extraordinary threat and the persistence of specific symptoms such as intrusion, avoidance, and physiological hyperarousal. Long-lasting traumata may lead to the development of complex syndromes or irreversible personality alterations. Chronic manifestations, psychiatric comorbidities, and psychosocial deficits are special risks in the course of post-traumatic stress disorders. Severe traumata are associated with complex neurobiological changes. Psychotherapeutic approaches are established as a three-stage model: stabilisation, trauma reorientation, and psychosocial reintegration. The additional use of psychotropic drugs should be oriented to the specific symptomatology.

  12. Peritraumatic reactions and posttraumatic stress disorder symptoms after psychiatric admission.

    PubMed

    Ladois-Do Pilar Rei, Agnès; Bui, Eric; Bousquet, Benjamin; Simon, Naomi M; Rieu, Julie; Schmitt, Laurent; Billard, Julien; Rodgers, Rachel; Birmes, Philippe

    2012-01-01

    The present study aimed to explore exposure to stressful events during a psychiatric admission and the predictive power of peritraumatic distress and dissociation in the development of posttraumatic stress disorder (PTSD) symptoms after exposure to such events. Psychiatric inpatients (N = 239) were asked to report exposure to stressful events during their admission within 48 hours of being admitted. Individuals reporting at least one stressful event during admission (n = 70, 29%) were assessed for peritraumatic dissociation and distress in relation to this event and, 5 weeks later, were reassessed for PTSD symptoms. Eight participants (12.3%) scored above the cutoff for probable PTSD. Multiple regression analyses revealed that peritraumatic distress was a significant predictor of 5-week PTSD symptoms. Our findings suggest that individuals experiencing increased peritraumatic distress in relation to a stressful event experienced during a psychiatric admission might be at risk of PTSD symptoms and might benefit from increased attention.

  13. Complex posttraumatic stress disorder: voices of healing.

    PubMed

    Spermon, Deborah; Darlington, Yvonne; Gibney, Paul

    2013-01-01

    In this article, we report on a phenomenological study of experiences of recovery of 7 women with histories of childhood maltreatment. We propose a model that recalls the Anglo-Franc etymological origins of rekeverer: to regain consciousness, health, or strength. Dimensions include development of a selfhood; tasks of connection and separation; regulation of overwhelming emotions; management of choices; and internalization of therapeutic relational dynamics. Based on the findings, we suggest that theory and research need to extend concepts of healing, add methodologies privileging victim/survivor voices, and revisit concepts such as neutrality and resistance as they apply to dissociative disorders. Practitioners should have specific training in trauma models, although they need to hold these theories lightly because therapeutic goals and pathways of change might well differ for each client. Integrated whole-of-government initiatives need to identify those at risk of abuse as early as possible, and provide response funding beyond assessment services.

  14. Stress and Support for Parents of Youth with Bipolar Disorder

    PubMed Central

    Nadkarni, Radha B.; Fristad, Mary A.

    2015-01-01

    Background This article reviews stress related to parenting a youth with bipolar disorder (BD), maladaptive coping, immunologic and physical functioning related to chronic stress; presents preliminary findings about the association between immune parameters and health conditions, mental health indices and interpersonal functioning in parents of children with mood disorders; and provides recommendations for stress management based on clinical trials of family-based psychoeducational psychotherapy (PEP). Data Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), Epstein Barr Virus (EBV), nutritional markers and measures of physical health, mental health and interpersonal functioning were collected from 26 parents of mood disordered children. Higher CRP was associated with more perceived stress, more depression, increased incidence of illness/ physical conditions, and lower albumin levels. Elevated IL-6 was associated with higher nicotine use. Limitations Sample size and demographics were restricted, limiting generalizability. Conclusion Pilot data are consistent with literature from adult caregivers, and suggest caregivers who are more stressed also evidence some signs of immune abnormality. Evidence-based strategies to support parents are discussed. PMID:22801289

  15. Can Molecular Hippocampal Alterations Explain Behavioral Differences in Prenatally Stressed Rats?

    EPA Science Inventory

    Studies in both humans and animals have shown that prenatal stress can alter cognitive function and other neurological behaviors in adult offspring. One possible underlying mechanism for this may lie with alterations in hippocampal gene expression. The present study examined geno...

  16. PHEOCHROMOCYTOMA: A CATECHOLAMINE AND OXIDATIVE STRESS DISORDER

    PubMed Central

    Pacak, Karel

    2012-01-01

    The WHO classification of endocrine tumors defines pheochromocytoma as a tumor arising from chromaffin cells in the adrenal medulla — an intra-adrenal paraganglioma. Closely related tumors of extra-adrenal sympathetic and parasympathetic paraganglia are classified as extra-adrenal paragangliomas. Almost all pheochromocytomas and paragangliomas produce catecholamines. The concentrations of catecholamines in pheochromocytoma tissues are enormous, potentially creating a volcano that can erupt at any time. Significant eruptions result in catecholamine storms called “attacks” or “spells”. Acute catecholamine crisis can strike unexpectedly, leaving traumatic memories of acute medical disaster that champions any intensive care unit. A very well-defined genotype-biochemical phenotype relationship exists, guiding proper and cost-effective genetic testing of patients with these tumors. Currently, the production of norepinephrine and epinephrine is optimally assessed by the measurement of their O-methylated metabolites, normetanephrine or metanephrine, respectively. Dopamine is a minor component, but some paragangliomas produce only this catecholamine or this together with norepinephrine. Methoxytyramine, the O-methylated metabolite of dopamine, is the best biochemical marker of these tumors. In those patients with equivocal biochemical results, a modified clonidine suppression test coupled with the measurement of plasma normetanephrine has recently been introduced. In addition to differences in catecholamine enzyme expression, the presence of either constitutive or regulated secretory pathways contributes further to the very unique mutation-dependent catecholamine production and release, resulting in various clinical presentations. Oxidative stress results from a significant imbalance between levels of prooxidants, generated during oxidative phosphorylation, and antioxidants. The gradual accumulation of prooxidants due to metabolic oxidative stress results in proto

  17. Markers of Oxidative Stress and Neuroprogression in Depression Disorder

    PubMed Central

    Vaváková, Magdaléna; Trebatická, Jana

    2015-01-01

    Major depression is multifactorial disorder with high prevalence and alarming prognostic in the nearest 15 years. Several mechanisms of depression are known. Neurotransmitters imbalance and imbalance between neuroprogressive and neuroprotective factors are observed in major depression. Depression is accompanied by inflammatory responses of the organism and consequent elevation of proinflammatory cytokines and increased lipid peroxidation are described in literature. Neuropsychiatric disorders including major depression are also associated with telomerase shortening, oxidative changes in nucleotides, and polymorphisms in several genes connected to metabolism of reactive oxygen species. Mitochondrion dysfunction is directly associated with increasing levels of oxidative stress. Oxidative stress plays significant role in pathophysiology of major depression via actions of free radicals, nonradical molecules, and reactive oxygen and nitrogen species. Products of oxidative stress represent important parameters for measuring and predicting of depression status as well as for determining effectiveness of administrated antidepressants. Positive effect of micronutrients, vitamins, and antioxidants in depression treatment is also reviewed. PMID:26078821

  18. Markers of Oxidative Stress and Neuroprogression in Depression Disorder.

    PubMed

    Vaváková, Magdaléna; Ďuračková, Zdeňka; Trebatická, Jana

    2015-01-01

    Major depression is multifactorial disorder with high prevalence and alarming prognostic in the nearest 15 years. Several mechanisms of depression are known. Neurotransmitters imbalance and imbalance between neuroprogressive and neuroprotective factors are observed in major depression. Depression is accompanied by inflammatory responses of the organism and consequent elevation of proinflammatory cytokines and increased lipid peroxidation are described in literature. Neuropsychiatric disorders including major depression are also associated with telomerase shortening, oxidative changes in nucleotides, and polymorphisms in several genes connected to metabolism of reactive oxygen species. Mitochondrion dysfunction is directly associated with increasing levels of oxidative stress. Oxidative stress plays significant role in pathophysiology of major depression via actions of free radicals, nonradical molecules, and reactive oxygen and nitrogen species. Products of oxidative stress represent important parameters for measuring and predicting of depression status as well as for determining effectiveness of administrated antidepressants. Positive effect of micronutrients, vitamins, and antioxidants in depression treatment is also reviewed.

  19. Folding propensity of intrinsically disordered proteins by osmotic stress

    SciTech Connect

    Mansouri, Amanda L.; Grese, Laura N.; Rowe, Erica L.; Pino, James C.; Chennubhotla, S. Chakra; Ramanathan, Arvind; O'Neill, Hugh Michael; Berthelier, Valerie; Stanley, Christopher B.

    2016-10-11

    Proteins imparted with intrinsic disorder conduct a range of essential cellular functions. To better understand the folding and hydration properties of intrinsically disordered proteins (IDPs), we used osmotic stress to induce conformational changes in nuclear co-activator binding domain (NCBD) and activator for thyroid hormone and retinoid receptor (ACTR). Osmotic stress was applied by the addition of small and polymeric osmolytes, where we discovered that water contributions to NCBD folding always exceeded those for ACTR. Both NCBD and ACTR were found to gain a-helical structure with increasing osmotic stress, consistent with their folding upon NCBD/ACTR complex formation. Using small-angle neutron scattering (SANS), we further characterized NCBD structural changes with the osmolyte ethylene glycol. Here a large reduction in overall size initially occurred before substantial secondary structural change. In conclusion, by focusing on folding propensity, and linked hydration changes, we uncover new insights that may be important for how IDP folding contributes to binding.

  20. Symptoms of acute posttraumatic stress disorder after intensive care.

    PubMed

    Wallen, Karen; Chaboyer, Wendy; Thalib, Lukman; Creedy, Debra K

    2008-11-01

    Admission to intensive care is often a sudden and unexpected event precipitated by a life-threatening condition, 2 determinants thought to influence the development of posttraumatic stress disorder. To identify the frequency of acute symptoms of posttraumatic stress disorder and to describe factors predictive of these symptoms in patients 1 month after discharge from intensive care. In this prospective cohort study, all patients meeting the inclusion criteria during the study period were invited to participate. Participants completed the Impact of Event Scale-Revised, and demographic and clinical data were accessed from an intensive care unit database. During a 9-month period, 114 of 137 patients who met the inclusion criteria consented to participate in the study, and 100 (88%) completed it. The mean total score on the Impact of Event Scale-Revised was 17.8 (SD, 13.4; possible range, 0-88). A total of 13 participants (13%) scored higher than the cutoff score for clinical posttraumatic stress disorder. Neither sex nor length of stay was predictive of acute symptoms of post-traumatic stress disorder. In multivariate analysis, the only independent predictor of symptoms was age. Patients younger than 65 years were 5.6 times (95% confidence interval, 1.17-26.89) more likely than those 65 years and older to report symptoms. The rate of symptoms of posttraumatic stress disorder 1 month after discharge from intensive care was relatively low. Consistent with findings of previous research, being younger than 65 years was the only independent predictor of symptoms.

  1. Associations between cytokines, endocrine stress response, and gastrointestinal symptoms in autism spectrum disorder.

    PubMed

    Ferguson, Bradley J; Marler, Sarah; Altstein, Lily L; Lee, Evon Batey; Mazurek, Micah O; McLaughlin, Aaron; Macklin, Eric A; McDonnell, Erin; Davis, Daniel J; Belenchia, Anthony M; Gillespie, Catherine H; Peterson, Catherine A; Bauman, Margaret L; Margolis, Kara Gross; Veenstra-VanderWeele, Jeremy; Beversdorf, David Q

    2016-11-01

    Many children and adolescents with autism spectrum disorder (ASD) have significant gastrointestinal (GI) symptoms, but the etiology is currently unknown. Some individuals with ASD show altered reactivity to stress and altered immune markers relative to typically-developing individuals, particularly stress-responsive cytokines including tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). Acute and chronic stress is associated with the onset and exacerbation of GI symptoms in those without ASD. The present study examined whether GI symptoms in ASD were associated with increases in cortisol, a stress-associated endocrine marker, and TNF-α and IL-6 in response to stress. As hypothesized, a greater amount of lower GI tract symptoms were significantly associated with post-stress cortisol concentration. The relationship between cortisol response to stress and GI functioning was greater for children who had a history of regressive autism. Exploratory analyses revealed significant correlations between cortisol response, intelligence, and inappropriate speech. In contrast, symptoms of the lower GI tract were not associated with levels of TNF-α or IL-6. Significant correlations were found, however, between TNF-α and IL-6 and irritability, socialization, and intelligence. These findings suggest that individuals with ASD and symptoms of the lower GI tract may have an increased response to stress, but this effect is not associated with concomitant changes in TNF-α and IL-6. The relationship between cortisol stress response and lower GI tract symptoms in children with regressive autism, as well as the relationships between cortisol, IL-6, and intelligence in ASD, warrant further investigation. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Stress during Adolescence Alters Palatable Food Consumption in a Context-Dependent Manner.

    PubMed

    Handy, Christine; Yanaga, Stephanie; Reiss, Avery; Zona, Nicole; Robinson, Emily; Saxton, Katherine B

    2016-01-01

    Food consumption and preferences may be shaped by exposure to stressful environments during sensitive periods in development, and even small changes in consumption can have important effects on long term health. Adolescence is increasingly recognized as a sensitive period, in which adverse experiences can alter development, but the specific programming effects that may occur during adolescence remain incompletely understood. The current study seeks to explore the effects of stress during late adolescence on consumption of a palatable, high-fat, high-sugar food in adulthood-under basal conditions, as well following acute stress. Male Long-Evans rats were exposed to a regimen of variable stress for seven days in late adolescence (PND 45-51). During the stress regimen, stressed animals gained significantly less weight than control animals, but weight in adulthood was unaffected by adolescent stress. Palatable food consumption differed between experimental groups, and the direction of effect depended on context; stressed rats ate significantly more palatable food than controls upon first exposure, but ate less following an acute stressor. Leptin levels and exploratory behaviors did not differ between stressed and non-stressed groups, suggesting that other factors regulate preference for a palatable food. Altered food consumption following adolescent stress suggests that rats remain sensitive to stress during late adolescence, and that adult feeding behavior may be affected by previous adverse experiences. Such programming effects highlight adolescence as a period of plasticity, with the potential to shape long term food consumption patterns and preferences.

  3. Stress during Adolescence Alters Palatable Food Consumption in a Context-Dependent Manner

    PubMed Central

    Handy, Christine; Yanaga, Stephanie; Reiss, Avery; Zona, Nicole; Robinson, Emily; Saxton, Katherine B.

    2016-01-01

    Food consumption and preferences may be shaped by exposure to stressful environments during sensitive periods in development, and even small changes in consumption can have important effects on long term health. Adolescence is increasingly recognized as a sensitive period, in which adverse experiences can alter development, but the specific programming effects that may occur during adolescence remain incompletely understood. The current study seeks to explore the effects of stress during late adolescence on consumption of a palatable, high-fat, high-sugar food in adulthood—under basal conditions, as well following acute stress. Male Long-Evans rats were exposed to a regimen of variable stress for seven days in late adolescence (PND 45–51). During the stress regimen, stressed animals gained significantly less weight than control animals, but weight in adulthood was unaffected by adolescent stress. Palatable food consumption differed between experimental groups, and the direction of effect depended on context; stressed rats ate significantly more palatable food than controls upon first exposure, but ate less following an acute stressor. Leptin levels and exploratory behaviors did not differ between stressed and non-stressed groups, suggesting that other factors regulate preference for a palatable food. Altered food consumption following adolescent stress suggests that rats remain sensitive to stress during late adolescence, and that adult feeding behavior may be affected by previous adverse experiences. Such programming effects highlight adolescence as a period of plasticity, with the potential to shape long term food consumption patterns and preferences. PMID:26872268

  4. [Interpersonal psychotherapy for work-related stress depressive disorders].

    PubMed

    Schramm, E; Berger, M

    2013-07-01

    In general work involves health promoting functions but can also have hazardous impacts on well-being. Due to a massive change in working conditions it has become increasingly more recognized that depressive disorders are highly prevalent at the workplace and that work stress belongs to the most common triggers of depressive disorders, particularly in men. It is relevant to differentiate between subjectively experienced burnout and clinical depression. The best investigated psychosocial work stressors include increased job demands in connection with low control possibilities and lack of gratification, interpersonal conflicts, role stress and social isolation. For the treatment of work-related clinical depression, an additional focus of interpersonal psychotherapy (IPT) of depression, namely "work-related stress and burnout experience" was conceptualized based on a vulnerability-stress model and the fact that work usually takes place in an interpersonal context. This new problem area focuses on role stress and conflicts at work and the reduction of stressful working conditions. Interpersonal psychotherapy has so far been useful for the treatment of depression due to problems at work; however, further studies are needed to evaluate the efficacy of this newly designed problem area.

  5. Pituitary adenylate cyclase activating polypeptide in stress-related disorders: data convergence from animal and human studies.

    PubMed

    Hammack, Sayamwong E; May, Victor

    2015-08-01

    The maladaptive expression and function of several stress-associated hormones have been implicated in pathological stress and anxiety-related disorders. Among these, recent evidence has suggested that pituitary adenylate cyclase activating polypeptide (PACAP) has critical roles in central neurocircuits mediating stress-related emotional behaviors. We describe the PACAPergic systems, the data implicating PACAP in stress biology, and how altered PACAP expression and signaling may result in psychopathologies. We include our work implicating PACAP signaling within the bed nucleus of the stria terminalis in mediating the consequences of stressor exposure and relatedly, describe more recent studies suggesting that PACAP in the central nucleus of the amygdala may impact the emotional aspects of chronic pain states. In aggregate, these results are consistent with data suggesting that PACAP dysregulation is associated with posttraumatic stress disorder in humans. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  6. Pituitary adenylate cyclase activating polypeptide in stress-related disorders: data convergence from animal and human studies

    PubMed Central

    May, Victor

    2014-01-01

    The maladaptive expression and function of several stress-associated hormones have been implicated in pathological stress- and anxiety-related disorders. Among these, recent evidence has suggested that pituitary adenylate cyclase activating polypeptide (PACAP) has critical roles in central neurocircuits mediating stress-related emotional behaviors. We describe the PACAPergic systems, the data implicating PACAP in stress biology and how altered PACAP expression and signaling may result in psychopathologies. We include our work implicating PACAP signaling within the bed nucleus of the stria terminalis (BNST) in mediating the consequences of stressor exposure and relatedly, describe more recent studies suggesting that PACAP in the central nucleus of the amygdala (CeA) may impact the emotional aspects of chronic pain states. In aggregate, these results are consistent with data suggesting that PACAP dysregulation is associated with post-traumatic stress disorder (PTSD) in humans. PMID:25636177

  7. Rumination predicts heightened responding to stressful life events in major depressive disorder and generalized anxiety disorder.

    PubMed

    Ruscio, Ayelet Meron; Gentes, Emily L; Jones, Jason D; Hallion, Lauren S; Coleman, Elizabeth S; Swendsen, Joel

    2015-02-01

    Although studies have documented heightened stress sensitivity in major depressive disorder (MDD) and generalized anxiety disorder (GAD), the mechanisms involved are poorly understood. One possible mechanism is the tendency to ruminate in response to stress. We used ecological momentary assessment to study ruminative thoughts after stressful events in 145 adults with MDD, GAD, comorbid MDD-GAD, or no psychopathology. Diagnosed individuals reported more event-related rumination than controls, even after adjusting for event stressfulness. Rumination was equally common in MDD and GAD and was especially severe among comorbid cases. More rumination immediately after the event predicted poorer affect, more maladaptive behavior, and more MDD and GAD symptoms at the next signal, even when pre-event levels of these variables were controlled. Rumination mediated, but did not moderate, the association of stress with affect and with symptoms. Stress-related rumination was more deleterious for diagnosed than healthy individuals, more intense for more severe clinical cases, and more persistent for cases with a greater temperamental vulnerability for emotional disorders. These results implicate rumination as a mechanism of stress sensitivity and suggest pathways through which it may maintain depression and anxiety in everyday life.

  8. Trichotillomania and post-traumatic stress disorder: a case study.

    PubMed

    Corso, Kent A; McGeary, Donald D

    2008-11-01

    This is a clinical case study of a 45-year-old, Caucasian male, active duty military officer. It demonstrates the short-term efficacy of habit-reversal training on the treatment of trichotillomania (TTM) in three 50-minute sessions, with concomitant, but unanticipated decreases in post-traumatic stress disorder (PTSD) symptoms and emotional distress as measured by the PTSD Checklist, Form PCL-M and OQ-45, respectively. This study discusses the benefits and limitations of such a short treatment for comorbid TTM and PTSD, while positing the relationship between the two disorders. Finally, it lends support for the classification of TTM as an anxiety disorder rather than an impulse-control disorder.

  9. Post-Traumatic Stress Disorder: A Psychiatric Defense

    PubMed Central

    Jordan, Harold W.; Howe, Gary L.; Gelsomino, Joe; Lockert, Edna W.

    1986-01-01

    Post-traumatic stress disorder (PTSD) is one of the anxiety disorders recently included in the Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III).1 The disorder refers to the psychological sequelae that may follow a significant stressor. The military has previously referred to PTSD as “war neurosis,” “shell shock,” and “combat neurosis.” PTSD has recently gained attention as a means of legal defense. As a defense, it may exist separately from “innocence by reason of insanity.” The authors review the literature, provide case vignettes exemplifying the clinical features, and present three additional cases that gained local and national notoriety because of their defense motions. The senior author served as an expert witness in these cases. Recommendations are given to readers who may in the future serve as expert witnesses or consultants in similar cases. PMID:3950984

  10. Bifidobacterium CECT 7765 modulates early stress-induced immune, neuroendocrine and behavioral alterations in mice.

    PubMed

    Moya-Pérez, A; Perez-Villalba, A; Benítez-Páez, A; Campillo, I; Sanz, Y

    2017-10-01

    Emerging evidence suggests that there is a window of opportunity within the early developmental period, when microbiota-based interventions could play a major role in modulating the gut-brain axis and, thereby, in preventing mood disorders. This study aims at evaluating the effects and mode of action of Bifidobacterium pseudocatenulatum CECT 7765 in a murine model of chronic stress induced by maternal separation (MS). C57Bl/6J male breast-fed pups were divided into four groups, which were subjected or not to MS and supplemented with placebo or B. pseudocatenulatum CECT7765 until postnatal period (P) 21 and followed-up until P41. Behavioral tests were performed and neuroendocrine parameters were analyzed including corticosterone, cytokine/chemokine concentrations and neurotransmitters. Microbiota was also analyzed in stools by 16S rRNA gene sequencing. B. pseudocatenulatum CECT 7765 administration attenuated some aspects of the excessive MS-induced stress response of the hypothalamic-pituitary-adrenal (HPA) axis, particularly corticosterone production at baseline and in response to subsequent acute stress in adulthood. B. pseudocatenulatum CECT 7765 also down-regulated MS-induced intestinal inflammation (reducing interferon gamma [IFN-γ]) and intestinal hypercatecholaminergic activity (reducing dopamine [DA] and adrenaline [A] concentrations) at P21. These effects have a long-term impact on the central nervous system (CNS) of adult mice since MS mice fed B. pseudocatenulatum CECT 7765 showed lower anxiety levels than placebo-fed MS mice, as well as normal neurotransmitter levels in the hypothalamus. The anti-inflammatory effect of B. pseudocatenulatum CECT 7765 seemed to be related to an improvement in glucocorticoid sensitivity in mesenteric lymph node immunocompetent cells at P21. The administration of B. pseudocatenulatum CECT 7765 to MS animals also reversed intestinal dysbiosis affecting the proportions of ten Operational Taxonomic Units (OTUs) at P21, which

  11. Alterations in the Vaginal Microbiome by Maternal Stress Are Associated With Metabolic Reprogramming of the Offspring Gut and Brain.

    PubMed

    Jašarević, Eldin; Howerton, Christopher L; Howard, Christopher D; Bale, Tracy L

    2015-09-01

    The neonate is exposed to the maternal vaginal microbiota during parturition, providing the primary source for normal gut colonization, host immune maturation, and metabolism. These early interactions between the host and microbiota occur during a critical window of neurodevelopment, suggesting early life as an important period of cross talk between the developing gut and brain. Because perturbations in the prenatal environment such as maternal stress increase neurodevelopmental disease risk, disruptions to the vaginal ecosystem could be a contributing factor in significant and long-term consequences for the offspring. Therefore, to examine the hypothesis that changes in the vaginal microbiome are associated with effects on the offspring gut microbiota and on the developing brain, we used genomic, proteomic and metabolomic technologies to examine outcomes in our mouse model of early prenatal stress. Multivariate modeling identified broad proteomic changes to the maternal vaginal environment that influence offspring microbiota composition and metabolic processes essential for normal neurodevelopment. Maternal stress altered proteins related to vaginal immunity and abundance of Lactobacillus, the prominent taxa in the maternal vagina. Loss of maternal vaginal Lactobacillus resulted in decreased transmission of this bacterium to offspring. Further, altered microbiota composition in the neonate gut corresponded with changes in metabolite profiles involved in energy balance, and with region- and sex-specific disruptions of amino acid profiles in the developing brain. Taken together, these results identify the vaginal microbiota as a novel factor by which maternal stress may contribute to reprogramming of the developing brain that may predispose individuals to neurodevelopmental disorders.

  12. Risk and resiliency factors in posttraumatic stress disorder

    PubMed Central

    Voges, Marcia A; Romney, David M

    2003-01-01

    Background Not everyone who experiences a trauma develops posttraumatic stress disorder (PTSD). The aim of this study was to determine the risk and resiliency factors for this disorder in a sample of people exposed to trauma. Method Twenty-five people who had developed PTSD following a trauma and 27 people who had not were asked to complete the Posttraumatic Stress Diagnostic Scale, the Coping Inventory for Stressful Situations, and the State-Trait Anxiety Inventory. In addition, they completed a questionnaire to provide information autobiographic and other information. Analysis Five variables that discriminated significantly between the two groups using chi-square analysis or t-tests were entered into a logistic regression equation as predictors, namely, being female, perceiving a threat to one's life, having a history of sexual abuse, talking to someone about the event, and the "intentionality" of the trauma. Results Only being female and perceiving a threat to one's life were significant predictors of PTSD. Taking base rates into account, 96.0% of participants with PTSD were correctly classified as having the disorder and 37.0% of participants without PTSD were correctly classified as not having the disorder, for an overall success rate of 65.4% Conclusions Because women are more likely than men to develop PTSD, more preventive measures should be directed towards them. The same is true for trauma victims (of both sexes) who feel that their life was in danger PMID:12780941

  13. It still hurts: altered endogenous opioid activity in the brain during social rejection and acceptance in major depressive disorder.

    PubMed

    Hsu, D T; Sanford, B J; Meyers, K K; Love, T M; Hazlett, K E; Walker, S J; Mickey, B J; Koeppe, R A; Langenecker, S A; Zubieta, J-K

    2015-02-01

    The μ-opioid receptor (MOR) system, well known for dampening physical pain, is also hypothesized to dampen 'social pain.' We used positron emission tomography scanning with the selective MOR radioligand [(11)C]carfentanil to test the hypothesis that MOR system activation (reflecting endogenous opioid release) in response to social rejection and acceptance is altered in medication-free patients diagnosed with current major depressive disorder (MDD, n=17) compared with healthy controls (HCs, n=18). During rejection, MDD patients showed reduced endogenous opioid release in brain regions regulating stress, mood and motivation, and slower emotional recovery compared with HCs. During acceptance, only HCs showed increased social motivation, which was positively correlated with endogenous opioid release in the nucleus accumbens, a reward structure. Altered endogenous opioid activity in MDD may hinder emotional recovery from negative social interactions and decrease pleasure derived from positive interactions. Both effects may reinforce depression, trigger relapse and contribute to poor treatment outcomes.

  14. Alteration of Gene Expression Profile in Niemann-Pick Type C Mice Correlates with Tissue Damage and Oxidative Stress

    PubMed Central

    Vázquez, Mary C.; del Pozo, Talía; Robledo, Fermín A.; Carrasco, Gonzalo; Pavez, Leonardo; Olivares, Felipe; González, Mauricio; Zanlungo, Silvana

    2011-01-01

    Background Niemann-Pick type C disease (NPC) is a neurovisceral lipid storage disorder mainly characterized by unesterified cholesterol accumulation in lysosomal/late endosomal compartments, although there is also an important storage for several other kind of lipids. The main tissues affected by the disease are the liver and the cerebellum. Oxidative stress has been described in various NPC cells and tissues, such as liver and cerebellum. Although considerable alterations occur in the liver, the pathological mechanisms involved in hepatocyte damage and death have not been clearly defined. Here, we assessed hepatic tissue integrity, biochemical and oxidative stress parameters of wild-type control (Npc1+/+; WT) and homozygous-mutant (Npc1−/−; NPC) mice. In addition, the mRNA abundance of genes encoding proteins associated with oxidative stress, copper metabolism, fibrosis, inflammation and cholesterol metabolism were analyzed in livers and cerebella of WT and NPC mice. Methodology/Principal Findings We analyzed various oxidative stress parameters in the liver and hepatic and cerebellum gene expression in 7-week-old NPC1-deficient mice compared with control animals. We found signs of inflammation and fibrosis in NPC livers upon histological examination. These signs were correlated with increased levels of carbonylated proteins, diminished total glutathione content and significantly increased total copper levels in liver tissue. Finally, we analyzed liver and cerebellum gene expression patterns by qPCR and microarray assays. We found a correlation between fibrotic tissue and differential expression of hepatic as well as cerebellar genes associated with oxidative stress, fibrosis and inflammation in NPC mice. Conclusions/Significance In NPC mice, liver disease is characterized by an increase in fibrosis and in markers associated with oxidative stress. NPC is also correlated with altered gene expression, mainly of genes involved in oxidative stress and fibrosis

  15. Altered brain structural networks in attention deficit/hyperactivity disorder children revealed by cortical thickness.

    PubMed

    Liu, Tian; Chen, Yanni; Li, Chenxi; Li, Youjun; Wang, Jue

    2017-01-18

    This study investigated the cortical thickness and topological features of human brain anatomical networks related to attention deficit/hyperactivity disorder. Data were collected from 40 attention deficit/hyperactivity disorder children and 40 normal control children. Interregional correlation matrices were established by calculating the correlations of cortical thickness between all pairs of cortical regions (68 regions) of the whole brain. Further thresholds were applied to create binary matrices to construct a series of undirected and unweighted graphs, and global, local, and nodal efficiencies were computed as a function of the network cost. These experimental results revealed abnormal cortical thickness and correlations in attention deficit/hyperactivity disorder, and showed that the brain structural networks of attention deficit/hyperactivity disorder subjects had inefficient small-world topological features. Furthermore, their topological properties were altered abnormally. In particular, decreased global efficiency combined with increased local efficiency in attention deficit/hyperactivity disorder children led to a disorder-related shift of the network topological structure toward regular networks. In addition, nodal efficiency, cortical thickness, and correlation analyses revealed that several brain regions were altered in attention deficit/hyperactivity disorder patients. These findings are in accordance with a hypothesis of dysfunctional integration and segregation of the brain in patients with attention deficit/hyperactivity disorder and provide further evidence of brain dysfunction in attention deficit/hyperactivity disorder patients by observing cortical thickness on magnetic resonance imaging.

  16. Attention deficit/hyperactivity disorder (ADHD) is associated with altered heart rate asymmetry.

    PubMed

    Tonhajzerová, I; Ondrejka, I; Farský, I; Višňovcová, Z; Mešťaník, M; Javorka, M; Jurko, A; Čalkovská, A

    2014-01-01

    Attention deficit/hyperactivity disorder (ADHD) is associated with complex neurocardiac integrity. We aimed to study heart rate time asymmetry as a nonlinear qualitative feature of heart rate variability indicating complexity of cardiac autonomic control at rest and in response to physiological stress (orthostasis) in children suffering from ADHD. Twenty boys with ADHD and 20 healthy age-matched boys at the age of 8 to 12 years were examined. The continuous ECG was recorded in a supine position and during postural change from lying to standing (orthostasis). Time irreversibility indices - Porta's (P%), Guzik's (G%) and Ehlers' (E) - were evaluated. Our analysis showed significantly reduced heart rate asymmetry indices at rest (P%: 49.8 % vs. 52.2 %; G%: 50.2 % vs. 53.2 %; p<0.02), and in response to orthostatic load (P%: 52.4 % vs. 54.5 %, G%: 52.3 % vs. 54.5 %; p<0.05) associated with tachycardia in ADHD children compared to controls. Concluding, our study firstly revealed the altered heart rate asymmetry pattern in children suffering from ADHD at rest as well as in response to posture change from lying to standing (orthostasis). These findings might reflect an abnormal complex cardiac regulatory system as a potential mechanism leading to later cardiac adverse outcomes in ADHD.

  17. Insulin resistance in brain alters dopamine turnover and causes behavioral disorders

    PubMed Central

    Kleinridders, Andre; Cai, Weikang; Cappellucci, Laura; Ghazarian, Armen; Collins, William R.; Vienberg, Sara G.; Pothos, Emmanuel N.; Kahn, C. Ronald

    2015-01-01

    Diabetes and insulin resistance are associated with altered brain imaging, depression, and increased rates of age-related cognitive impairment. Here we demonstrate that mice with a brain-specific knockout of the insulin receptor (NIRKO mice) exhibit brain mitochondrial dysfunction with reduced mitochondrial oxidative activity, increased levels of reactive oxygen species, and increased levels of lipid and protein oxidation in the striatum and nucleus accumbens. NIRKO mice also exhibit increased levels of monoamine oxidase A and B (MAO A and B) leading to increased dopamine turnover in these areas. Studies in cultured neurons and glia cells indicate that these changes in MAO A and B are a direct consequence of loss of insulin signaling. As a result, NIRKO mice develop age-related anxiety and depressive-like behaviors that can be reversed by treatment with MAO inhibitors, as well as the tricyclic antidepressant imipramine, which inhibits MAO activity and reduces oxidative stress. Thus, insulin resistance in brain induces mitochondrial and dopaminergic dysfunction leading to anxiety and depressive-like behaviors, demonstrating a potential molecular link between central insulin resistance and behavioral disorders. PMID:25733901

  18. Posttraumatic Stress Disorder's Underlying Dimensions and Their Relation With Impulsivity Facets.

    PubMed

    Contractor, Ateka A; Armour, Cherie; Forbes, David; Elhai, Jon D

    2016-01-01

    Research indicates a significant relationship between posttraumatic stress disorder (PTSD) and impulsivity (Kotler, Julian, Efront, and Amir, J Nerv Ment Dis 189:162-167, 2001; Ledgerwood and Petry, J Trauma Stress 19:411-416, 2006). The present study assessed relations between PTSD symptom clusters and impulsivity subscales in an effort to assess the specific impulsivity component most related to PTSD's alterations in arousal/reactivity and alterations in mood/cognitions symptoms. In the current study, the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, and the UPPS Impulsivity Scale were administered to a sample of 412 nonclinical subjects with a trauma history. Results indicated that PTSD's alterations in arousal/reactivity and mood/cognition factors were most related to impulsivity's sensation-seeking tendency compared with other impulsivity components. Results highlight the importance of assessing and addressing (1) sensation-seeking tendencies and (2) urges to act impulsively when experiencing negative affect in trauma treatment. Furthermore, it is possible that sensation-seeking tendencies are primarily driving the comorbidity between PTSD and certain impulsive behaviors.

  19. Interplay of endoplasmic reticulum stress and autophagy in neurodegenerative disorders

    PubMed Central

    Cai, Yu; Arikkath, Jyothi; Yang, Lu; Guo, Ming-Lei; Periyasamy, Palsamy; Buch, Shilpa

    2016-01-01

    ABSTRACT The common underlying feature of most neurodegenerative diseases such as Alzheimer disease (AD), prion diseases, Parkinson disease (PD), and amyotrophic lateral sclerosis (ALS) involves accumulation of misfolded proteins leading to initiation of endoplasmic reticulum (ER) stress and stimulation of the unfolded protein response (UPR). Additionally, ER stress more recently has been implicated in the pathogenesis of HIV-associated neurocognitive disorders (HAND). Autophagy plays an essential role in the clearance of aggregated toxic proteins and degradation of the damaged organelles. There is evidence that autophagy ameliorates ER stress by eliminating accumulated misfolded proteins. Both abnormal UPR and impaired autophagy have been implicated as a causative mechanism in the development of various neurodegenerative diseases. This review highlights recent advances in the field on the role of ER stress and autophagy in AD, prion diseases, PD, ALS and HAND with the involvement of key signaling pathways in these processes and implications for future development of therapeutic strategies. PMID:26902584

  20. Is interoceptive awareness really altered in somatoform disorders? Testing competing theories with two paradigms of heartbeat perception.

    PubMed

    Schaefer, Manuela; Egloff, Boris; Witthöft, Michael

    2012-08-01

    Alterations in the perception of body signals (i.e., interoceptive awareness [IA]) are considered crucial for the development and maintenance of somatoform disorders (SFDs). However, competing theories come to different conclusions about whether IA is increased or decreased in SFDs. The present study investigated IA in 23 patients with SFDs (as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) and in 27 healthy controls. IA was reliably assessed with two well-established heartbeat perception paradigms (heartbeat discrimination task and mental tracking task). The results of both paradigms showed no evidence for increased IA in patients with SFDs. Correlational analyses revealed that having a higher number of somatoform symptoms was significantly linked to lower (rather than higher) IA in SFDs. These findings are in line with recent cognitive approaches to SFDs that stress the importance of biased schema-guided processing of interoceptive information. PsycINFO Database Record (c) 2012 APA, all rights reserved.

  1. Role of neurotrophic factor alterations in the neurodegenerative process in HIV associated neurocognitive disorders.

    PubMed

    Fields, Jerel; Dumaop, Wilmar; Langford, T D; Rockenstein, Edward; Masliah, E

    2014-03-01

    Migration of HIV infected cells into the CNS is associated with a spectrum of neurological disorders, ranging from milder forms of HIV-associated neurocognitive disorders (HAND) to HIV-associated dementia (HAD). These neuro-psychiatric syndromes are related to the neurodegenerative pathology triggered by the release of HIV proteins and cytokine/chemokines from monocytes/macrophages into the CNS -a condition known as HIV encephalitis (HIVE). As a result of more effective combined anti-retroviral therapy patients with HIV are living longer and thus the frequency of HAND has increased considerably, resulting in an overlap between the neurodegenerative pathology associated with HIV and that related to aging. In fact, HIV infection is believed to hasten the aging process. The mechanisms through which HIV and aging lead to neurodegeneration include: abnormal calcium flux, excitotoxicity, signaling abnormalities, oxidative stress and autophagy defects. Moreover, recent studies have shown that defects in the processing and transport of neurotrophic factors such as fibroblast growth factors (FGFs), neural growth factor (NGF) and brain-derived growth factor (BDNF) might also play a role. Recent evidence implicates alterations in neurotrophins in the pathogenesis of neurodegeneration associated with HAND in the context of aging. Here, we report FGF overexpression curtails gp120-induced neurotoxicity in a double transgenic mouse model. Furthermore, our data show disparities in brain neurotrophic factor levels may be exacerbated in HIV patients over 50 years of age. In this review, we discuss the most recent findings on neurotrophins and HAND in the context of developing new therapies to combat HIV infection in the aging population.

  2. Subregional Shape Alterations in the Amygdala in Patients with Panic Disorder.

    PubMed

    Yoon, Sujung; Kim, Jieun E; Kim, Geon Ha; Kang, Hee Jin; Kim, Bori R; Jeon, Saerom; Im, Jooyeon Jamie; Hyun, Heejung; Moon, Sohyeon; Lim, Soo Mee; Lyoo, In Kyoon

    2016-01-01

    The amygdala has been known to play a pivotal role in mediating fear-related responses including panic attacks. Given the functionally distinct role of the amygdalar subregions, morphometric measurements of the amygdala may point to the pathophysiological mechanisms underlying panic disorder. The current study aimed to determine the global and local morphometric alterations of the amygdala related to panic disorder. Volumetric and surface-based morphometric approach to high-resolution three-dimensional T1-weighted images was used to examine the structural variations of the amygdala, with respect to extent and location, in 23 patients with panic disorder and 31 matched healthy individuals. There were no significant differences in bilateral amygdalar volumes between patients with panic disorder and healthy individuals despite a trend-level right amygdalar volume reduction related to panic disorder (right, β = -0.23, p = 0.09, Cohen's d = 0.51; left, β = -0.18, p = 0.19, Cohen's d = 0.45). Amygdalar subregions were localized into three groups including the superficial, centromedial, and laterobasal groups based on the cytoarchitectonically defined probability map. Surface-based morphometric analysis revealed shape alterations in the laterobasal and centromedial groups of the right amygdala in patients with panic disorder (false discovery rate corrected p < 0.05). The current findings suggest that subregion-specific shape alterations in the right amygdala may be involved in the development and maintenance of panic disorder, which may be attributed to the cause or effects of amygdalar hyperactivation.

  3. Do polyamines alter the sensitivity of lichens to nitrogen stress?

    PubMed

    Pirintsos, S A; Munzi, S; Loppi, S; Kotzabasis, K

    2009-07-01

    The sensitivity of lichens measuring photosynthetic efficiency and polyamines as modulator of nitrogen stress tolerance was investigated. Two lichen species with a markedly different tolerance to nitrogen compounds, namely Evernia prunastri (L.) Ach. and Xanthoria parietina (L.) Th.Fr., were incubated with deionized water (control) and solutions of KNO(3), NH(4)NO(3) and (NH(4))(2)SO(4) and then exposed to different light conditions. The F(v)/F(m) parameter (maximum quantum efficiency of photosystem II) was used as stress indicator. The results showed that F(v)/F(m) values, in the produced experimental conditions, were independent from the light gradient. Photosynthetic efficiency of E. prunastri was impaired by high ammonium concentrations, while nitrate had no effect; X. parietina was hardly influenced by nitrogen compounds. External supply of polyamines reduced the sensitivity of E. prunastri, while polyamine inhibitors reduced the tolerance of X. parietina to NH(4)(+), suggesting that polyamines play an important role in modulating the sensitivity/tolerance to nitrogen stress.

  4. Oxidative stress and an altered methionine metabolism in alcoholism.

    PubMed

    Bleich, S; Spilker, K; Kurth, C; Degner, D; Quintela-Schneider, M; Javaheripour, K; Rüther, E; Kornhuber, J; Wiltfang, J

    2000-11-03

    The exact mechanism of brain atrophy in patients with chronic alcoholism remains unknown. There is growing evidence that chronic alcoholism is associated with oxidative stress and with a derangement in sulphur amino acid metabolism (e.g. ethanol-induced hyperhomocysteinemia). Furthermore, it has been reported that homocysteine induces neuronal cell death by stimulating N-methyl-D-aspartate receptors as well as by producing free radicals. To further evaluate this latter hypothesis we analysed serum levels of both homocysteine and markers of oxidative stress (malondialdehyde) in alcoholic patients who underwent withdrawal from alcohol. Homocysteine and malondialdehyde were quantified by high performance liquid chromatography (HPLC) in serum samples of 35 patients (active drinkers). There was a significant correlation (P<0. 01) between blood alcohol concentration and elevated homocysteine (Spearman's r=0.71) and malondialdehyde (r=0.90) levels on admission. In addition, homocysteine and malondialdehyde levels were found to be significant decreased after 3 days of withdrawal treatment (Wilcoxon test: homocysteine, Z=-5.127; malondialdehyde, Z=-3.120; P<0.01). We postulate that excitatory neurotransmitters and mechanisms of oxidative stress in patients with chronic alcoholism may partly mediate excitotoxic neuronal damage and hereby cause brain shrinkage.

  5. A short review on the psychoneuroimmunology of posttraumatic stress disorder: from risk factors to medical comorbidities.

    PubMed

    Pace, Thaddeus W W; Heim, Christine M

    2011-01-01

    Posttraumatic stress disorder (PTSD) is a serious and debilitating condition with a prevalence rate of approximately 8% in the United States. Given the number of veterans returning from conflicts around the globe with PTSD, and the substantial number of civilians experiencing traumas, new perspectives on the biology of PTSD are needed. Based on the concept that PTSD is a disorder of stress response systems, numerous studies have suggested changes in hypothalamic-pituitary-adrenal (HPA) axis and sympathetic-adrenal-medullary (SAM) system function in patients with PTSD. Given that both glucocorticoids and catecholamines exert powerful effects on the immune system, it is surprising that relatively few studies have examined immune changes in patients with PTSD. Moreover, patients with PTSD are known to have increased rates of comorbidity with somatic disorders that involve immune and inflammatory processes. Patients with PTSD have been found to exhibit a number of immune changes including increased circulating inflammatory markers, increased reactivity to antigen skin tests, lower natural killer cell activity, and lower total T lymphocyte counts. Studies with humans and rodents suggest that certain proinflammatory cytokines are able to induce neurochemical and behavioral changes that resemble some key features of PTSD. This short article reviews immune alterations in PTSD, and considers possible mechanisms by which such changes may be related to neuroendocrine alterations and medical comorbidities of PTSD.

  6. Disorder of extreme stress not otherwise specified (DESNOS) in Croatian war veterans with posttraumatic stress disorder: case-control study

    PubMed Central

    Nemčić-Moro, Iva; Frančišković, Tanja; Britvić, Dolores; Klarić, Miro; Zečević, Iva

    2011-01-01

    Aim To determine the presence of disorder of extreme stress not otherwise specified (DESNOS) in Croatian war veterans who suffer from combat-related posttraumatic stress disorder (PTSD). Methods The research included 247 veterans of the 1991-1995 war in Croatia who suffered from PTSD and were psychiatrically examined at four clinical centers in Croatia during a month in 2008. It was based on the following self-assessment instruments: The Harvard Trauma Questionnaire (HTQ): Croatian Version, the Structured Interview for Disorder of Extreme Stress (SIDES-SR), and the Mini International Neuropsychiatric Interview (MINI) Results Based on the SIDES-SR results, we formed two groups of participants: the group with PTSD (N = 140) and the group with both PTSD and DESNOS (N = 107). Forty three percent of participants met the criteria for DESNOS. There was a significant difference in the intensity of posttraumatic symptoms between the group with both PTSD and DESNOS and the group with PTSD only (U = 3733.5, P = 0.001). Respondents who suffered from both PTSD and DESNOS also reported a significantly larger number of comorbid mental disorders (U = 1123.5, P = 0.049) and twice more frequently reported comorbid depression with melancholic features (OR = 2.109, P = 0.043), social phobia (OR = 2.137, P = 0.036), or panic disorder (OR = 2.208, P = 0.015). Conclusion Our results demonstrate that PTSD and DESNOS can occur in comorbidity, which is in contrast with the ICD-10 criteria. A greater intensity of symptoms and a more frequent comorbidity with other psychiatric disorders, especially depression, panic disorder, and social phobia require additional therapy interventions in the treatment processes. PMID:21853545

  7. Postanesthesia emergence in patients with post-traumatic stress disorder.

    PubMed

    Umholtz, Matthew; Cilnyk, John; Wang, Christopher K; Porhomayon, Jahan; Pourafkari, Leili; Nader, Nader D

    2016-11-01

    Recovery from anesthesia may be complicated with development of severe panic symptoms and anxiety. Preexisting anxiety disorder has been reported as a risk factor for development of these symptoms. We aimed to examine the frequency of emergence delirium (EDL) among veterans diagnosed with posttraumatic stress disorders (PTSDs). Retrospective cohort. Postoperative recovery area. Perioperative information of 1763 consecutive patients who underwent a surgical procedure requiring general anesthesia were collected. The patients were grouped on the basis of previous diagnosis of PTSD. A total of 317 patients were identified with a positive history of PTSD and were compared to 1446 patients without such a history for the occurrence of EDL in the postanesthesia care unit (PACU) as the primary endpoint. Duration of stay in PACU in minutes and the frequency of hospital admission were the secondary endpoints. Multivariate binary logistic regression analysis was performed to identify the predictors of EDL among the veteran population. Emergence delirium was reported in 37 cases (2.1%) after general anesthesia. Fifteen (4.7%) of 317 patients with PTSD and 22 (1.5%) of 1446 patients without history of PTSD demonstrated symptoms related to EDL in the PACU (P=.002). After propensity matching, there were 8 patients with EDL in the PTSD group whereas there were only 2 patients with EDL among controls. Posttraumatic stress disorder was also an independent predictor of EDL in multivariate analysis with an odds ratio of 6.66 and a 95% confidence interval of 2.04 to 21.72 (P=.002). Posttraumatic stress disorder independently predicted the frequency of EDL even after correcting for preexisting depression and anxiety disorders. A relatively longer duration of PACU stay in PTSD patients may reflect raised awareness of the health care workers about this debilitating mental disorder. Published by Elsevier Inc.

  8. Trauma exposure and post-traumatic stress disorder in bipolar disorder.

    PubMed

    Assion, Hans-Jörg; Brune, Nils; Schmidt, Nadja; Aubel, Thomas; Edel, Marc-Andreas; Basilowski, Miriam; Juckel, Georg; Frommberger, Ulrich

    2009-12-01

    There is a lack of data about post-traumatic stress disorder (PTSD) in European bipolar patients compared to the US-population. This study was conducted to ascertain the rates and types of traumatic events and PTSD in bipolar-I disorder. Euthymic bipolar patients were screened for lifetime diagnosis of PTSD using the Post-Traumatic Stress Diagnostic Scale and the Clinician Administered Post-traumatic Stress Disorder Scale. A total of 74 patients (m = 30, f = 44) with diagnosis of bipolar-I disorder were assessed. 37 patients (50%) reported no trauma, 22 patients (29.7%) experienced traumatic events without diagnosis of PTSD and 15 patients (20.3%) had comorbid PTSD. Bipolar PTSD patients were at higher risk to be exposed to physical violence, parental disregard, alcohol dependence of parents, sexual assault by a family member or acquaintance. The number of siblings was higher and they had higher scores on the Hamilton Depression Rating Scale and the Global Assessment of Functioning Scale. Bipolar patients are more likely to experience traumatic events and PTSD is a relevant comorbid disorder. PTSD is associated with an increased illness severity of bipolar disorder.

  9. Mechanical Alterations Associated with Repeated Treadmill Sprinting under Heat Stress

    PubMed Central

    Brocherie, Franck; Morin, Jean-Benoit; Racinais, Sébastien; Millet, Grégoire P.; Périard, Julien D.

    2017-01-01

    Purpose Examine the mechanical alterations associated with repeated treadmill sprinting performed in HOT (38°C) and CON (25°C) conditions. Methods Eleven recreationally active males performed a 30-min warm-up followed by three sets of five 5-s sprints with 25-s recovery and 3-min between sets in each environment. Constant-velocity running for 1-min at 10 and 20 km.h-1 was also performed prior to and following sprinting. Results Mean skin (37.2±0.7 vs. 32.7±0.8°C; P<0.001) and core (38.9±0.2 vs. 38.8±0.3°C; P<0.05) temperatures, together with thermal comfort (P<0.001) were higher following repeated sprinting in HOT vs. CON. Step frequency and vertical stiffness were lower (-2.6±1.6% and -5.5±5.5%; both P<0.001) and contact time (+3.2±2.4%; P<0.01) higher in HOT for the mean of sets 1–3 compared to CON. Running distance per sprint decreased from set 1 to 3 (-7.0±6.4%; P<0.001), with a tendency for shorter distance covered in HOT vs. CON (-2.7±3.4%; P = 0.06). Mean vertical (-2.6±5.5%; P<0.01), horizontal (-9.1±4.4%; P<0.001) and resultant ground reaction forces (-3.0±2.8%; P<0.01) along with vertical stiffness (-12.9±2.3%; P<0.001) and leg stiffness (-8.4±2.7%; P<0.01) decreased from set 1 to 3, independently of conditions. Propulsive power decreased from set 1 to 3 (-16.9±2.4%; P<0.001), with lower propulsive power values in set 2 (-6.6%; P<0.05) in HOT vs. CON. No changes in constant-velocity running patterns occurred between conditions, or from pre-to-post repeated-sprint exercise. Conclusions Thermal strain alters step frequency and vertical stiffness during repeated sprinting; however without exacerbating mechanical alterations. The absence of changes in constant-velocity running patterns suggests a strong link between fatigue-induced velocity decrements during sprinting and mechanical alterations. PMID:28146582

  10. Oxidative metabolism is associated with physiological disorders in fruits stored under multiple environmental stresses.

    PubMed

    Lum, Geoffrey B; Shelp, Barry J; DeEll, Jennifer R; Bozzo, Gale G

    2016-04-01

    In combination with low temperature, controlled atmosphere storage and 1-methylcyclopropene (ethylene antagonist) application are used to delay senescence of many fruits and vegetables. Controlled atmosphere consists of low O2 and elevated CO2. When sub-optimal partial pressures are used, these practices represent multiple abiotic stresses that can promote the development of physiological disorders in pome fruit, including flesh browning and cavities, although there is some evidence for genetic differences in susceptibility. In the absence of surface disorders, fruit with flesh injuries are not easily distinguished from asymptomatic fruit until these are consumed. Oxidative stress metabolites tend to accumulate (e.g., γ-aminobutyrate) or rapidly decline (e.g., ascorbate and glutathione) in vegetative tissues exposed to hypoxic and/or elevated CO2 environments. Moreover, these phenomena can be associated with altered energy and redox status. Biochemical investigations of Arabidopsis and tomato plants with genetically-altered levels of enzymes associated with the γ-aminobutyrate shunt and the ascorbate-glutathione pathway indicate that these metabolic processes are functionally related and critical for dampening the oxidative burst in vegetative and fruit tissues, respectively. Here, we hypothesize that γ-aminobutyrate accumulation, as well energy and antioxidant depletion are associated with the development of physiological injury in pome fruit under multiple environmental stresses. An improved understanding of this relationship could assist in maintaining the quality of stored fruit. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Trauma Type and Posttraumatic Stress Disorder as Predictors of Parenting Stress in Trauma-Exposed Mothers.

    PubMed

    Wilson, Christina K; Padrón, Elena; Samuelson, Kristin W

    2017-02-01

    Trauma exposure is associated with various parenting difficulties, but few studies have examined relationships between trauma, posttraumatic stress disorder (PTSD), and parenting stress. Parenting stress is an important facet of parenting and mediates the relationship between parental trauma exposure and negative child outcomes (Owen, Thompson, & Kaslow, 2006). We examined trauma type (child maltreatment, intimate partner violence, community violence, and non-interpersonal traumas) and PTSD symptoms as predictors of parenting stress in a sample of 52 trauma-exposed mothers. Community violence exposure and PTSD symptom severity accounted for significant variance in parenting stress. Further analyses revealed that emotional numbing was the only PTSD symptom cluster accounting for variance in parenting stress scores. Results highlight the importance of addressing community violence exposure and emotion regulation difficulties with trauma-exposed mothers.

  12. Stresses of passage, balms of resettlement, and posttraumatic stress disorder among Sri Lankan Tamils in Canada.

    PubMed

    Beiser, Morton; Simich, Laura; Pandalangat, Nalini; Nowakowski, Matilda; Tian, Fu

    2011-06-01

    To explore the salience of pre- and postmigration stresses as risk factors for posttraumatic stress disorder (PTSD) and to identify resilience factors and explore their mental health salience. We conducted a mental health survey of 1603 Sri Lankan Tamils in Toronto, incorporating the World Health Organization Composite International Diagnostic Interview for PTSD. According to the International Classification of Diseases, 10th Revision, criteria, lifetime prevalence for PTSD was 12%; according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria it was 5.8%. Female sex and the number of stresses of passage increased the probability of PTSD, whereas satisfaction with life and the availability of nonfamily social relations reduced it. Consideration of pre- and postmigration stresses of passage and of the nature of resilience contributes to an improved understanding of PTSD among refugees.

  13. New drug development for post-traumatic stress disorder.

    PubMed

    Berlant, Jeffrey

    2003-01-01

    US FDA approval of two serotonin-selective reuptake inhibitor (SSRI) agents for post-traumatic stress disorder (PTSD) has created new opportunities for drug development. This follows many years of exploring the potential utility of several classes of psychotropic agents for this very common, yet under-recognized and under-treated disorder. This review examines some of the basic neurobiological abnormalities observed in PTSD and summarizes open and controlled drug trials for major classes of medications, including SSRIs, other antidepressants, atypical neuroleptics, noradrenergic modulators and anticonvulsants, while critically evaluating the extent of effectiveness of these agents and reviewing unmet gaps in therapeutic need.

  14. Stress in obesity and associated metabolic and cardiovascular disorders.

    PubMed

    Holvoet, Paul

    2012-01-01

    Obesity has significant implications for healthcare, since it is a major risk factor for both type 2 diabetes and the metabolic syndrome. This syndrome is a common and complex disorder combining obesity, dyslipidemia, hypertension, and insulin resistance. It is associated with high atherosclerotic cardiovascular risk, which can only partially be explained by its components. Therefore, to explain how obesity contributes to the development of metabolic and cardiovascular disorders, more and better insight is required into the effects of personal and environmental stress on disease processes. In this paper, we show that obesity is a chronic inflammatory disease, which has many molecular mechanisms in common with atherosclerosis. Furthermore, we focus on the role of oxidative stress associated with obesity in the development of the metabolic syndrome. We discuss how several stress conditions are related to inflammation and oxidative stress in association with obesity and its complications. We also emphasize the relation between stress conditions and the deregulation of epigenetic control mechanisms by means of microRNAs and show how this impairment further contributes to the development of obesity, closing the vicious circle. Finally, we discuss the limitations of current anti-inflammation and antioxidant therapy to treat obesity.

  15. TEMPOROMANDIBULAR DYSFUNCTION, STRESS AND COMMON MENTAL DISORDER IN UNIVERSITY STUDENTS

    PubMed Central

    Augusto, Viviane Gontijo; Perina, Keity Cristina Bueno; Penha, Daniel Silva Gontijo; dos Santos, Daiane Carolina Alves; Oliveira, Valéria Aparecida Souza

    2016-01-01

    ABSTRACT Objective: To evaluate the prevalence of temporomandibular dysfunction (TMD) and its association with perceived stress and common mental disorder (CMD) in academic students. Methods: This is s transversal observational study conducted at Universidade de Minas Gerais, Divinópolis Unit, in health science courses. To investigate the prevalence of TMD, the anamnestic index by Fonseca was used. Stress was assessed by the perceived stress scale, translated and adapted for the Brazilian population in 2006. To track CMD, we used the Self-Reporting Questionnaire (SRQ-20). Data were analyzed using SPSS version 13.0, adopting a 5% significance level. Results: The prevalence of TMD in the sample was 71.9%, distributed as follows: Light TMD (50.0%), moderate (16.4%) and severe (5.5%), being more frequent among women (76.4%). Common mental disorders were present in 29.9% of participants. The average perceived stress was 30.9. Conclusion: The results of this study allow us to conclude that there is a statistically significant correlation between TMD and variables such as parafunctional habits, perceived stress and CMD. Level of Evidence II, Development of diagnostic criteria on consecutive patients (with universally applied reference "gold" standard). PMID:28924361

  16. Stress in Obesity and Associated Metabolic and Cardiovascular Disorders

    PubMed Central

    Holvoet, Paul

    2012-01-01

    Obesity has significant implications for healthcare, since it is a major risk factor for both type 2 diabetes and the metabolic syndrome. This syndrome is a common and complex disorder combining obesity, dyslipidemia, hypertension, and insulin resistance. It is associated with high atherosclerotic cardiovascular risk, which can only partially be explained by its components. Therefore, to explain how obesity contributes to the development of metabolic and cardiovascular disorders, more and better insight is required into the effects of personal and environmental stress on disease processes. In this paper, we show that obesity is a chronic inflammatory disease, which has many molecular mechanisms in common with atherosclerosis. Furthermore, we focus on the role of oxidative stress associated with obesity in the development of the metabolic syndrome. We discuss how several stress conditions are related to inflammation and oxidative stress in association with obesity and its complications. We also emphasize the relation between stress conditions and the deregulation of epigenetic control mechanisms by means of microRNAs and show how this impairment further contributes to the development of obesity, closing the vicious circle. Finally, we discuss the limitations of current anti-inflammation and antioxidant therapy to treat obesity. PMID:24278677

  17. Combat Blast Injuries: Injury Severity and Posttraumatic Stress Disorder Interaction on Career Outcomes in Male Servicemembers

    DTIC Science & Technology

    2013-01-01

    Naval Health Research Center Combat Blast Injuries: Injury Severity and Posttraumatic Stress Disorder Interaction on Career Outcomes in Male...injuries: Injury severity and posttraumatic stress disorder interaction on career outcomes in male servicemembers Susan L. Eskridge, PT, PhD;1...proportions were higher in those with posttraumatic stress disorder (PTSD) than in those without PTSD. There was a significant interaction between PTSD

  18. Assessing Post Traumatic Stress Disorder and PTSD Symptomatology in U. S. Army Personnel

    DTIC Science & Technology

    1994-06-11

    Post Traumatic Stress Disorder and...P.;T., Adler, A.,B.; Vaitkus, M.,A. Country: USA Title: Assessing Post Traumatic Stress Disorder and PTSD Symptomatology in U.S. Army Personnel This...T POST - TRAUMATIC STRESS , DISORDER ’A Experience an event outside the range of usual human experience B. Persistently reexperience the traumatic

  19. Valproate in combat-related posttraumatic stress disorder.

    PubMed

    Fesler, F A

    1991-09-01

    The symptoms of posttraumatic stress disorder (PTSD) suggest sympathetic nervous system hyperarousal and hyperreactivity. Pathophysiology of this condition may include stress-activated limbic kindling. Antikindling agents lithium and carbamazepine have been found effective for PTSD symptoms of intrusive reexperiencing and increased arousal. These facts suggest that valproate, another drug shown to interfere with limbic kindling, could also be effective for treatment of PTSD. An open clinical trial of valproate was conducted in 16 Vietnam veterans diagnosed with DSM-III-R combat-related PTSD. Ten of 16 patients showed significant improvement, especially in hyperarousal/hyperreactivity symptoms. The efficacy of valproate in the treatment of PTSD should be rigorously studied.

  20. Work stress and posttraumatic stress disorder in ED nurses/personnel.

    PubMed

    Laposa, Judith M; Alden, Lynn E; Fullerton, Louise M

    2003-02-01

    Work-related stress in the emergency department previously has been linked to depression and burnout; however, these findings have not been extended to the development of anxiety disorders, such as posttraumatic stress disorder (PTSD). Three sets of factors have been shown to contribute to stress in ED personnel: organizational characteristics, patient care, and the interpersonal environment. The current study addressed whether an association exists between sources of workplace stress and PTSD symptoms. Respondents were 51 ED personnel from a hospital in a large Canadian urban center. The majority of respondents were emergency nurses. Respondents completed questionnaires measuring PTSD and sources of work stress and answered a series of questions regarding work-related responses to stress or trauma. Interpersonal conflict was significantly associated with PTSD symptoms. The majority of respondents (67%) believed they had received inadequate support from hospital administrators following the traumatic incident and 20% considered changing jobs as a result of the trauma. Only 18% attended critical incident stress debriefing and none sought outside help for their distress. These findings underscore the need for hospital administrations to be aware of the extent of workplace stress and PTSD symptoms in their employees. Improving the interpersonal climate in the workplace may be useful in ameliorating PTSD symptoms.

  1. ER stress signaling and neurodegeneration: At the intersection between Alzheimer's disease and Prion-related disorders.

    PubMed

    Torres, Mauricio; Matamala, José Manuel; Duran-Aniotz, Claudia; Cornejo, Victor Hugo; Foley, Andrew; Hetz, Claudio

    2015-09-02

    Alzheimer's and Prion diseases are two neurodegenerative conditions sharing different pathophysiological characteristics. Disease symptoms are associated with the abnormal accumulation of protein aggregates, which are generated by the misfolding and oligomerization of specific proteins. Recent functional studies uncovered a key role of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in the occurrence of synaptic dysfunction and neurodegeneration in Prion-related disorders and Alzheimer's disease. Here we review common pathological features of both diseases, emphasizing the link between amyloid formation, its pathogenesis and alterations in ER proteostasis. The potential benefits of targeting the UPR as a therapeutic strategy is also discussed.

  2. Amyotrophic lateral sclerosis-linked FUS/TLS alters stress granule assembly and dynamics

    PubMed Central

    2013-01-01

    Background Amyotrophic lateral sclerosis (ALS)-linked fused in sarcoma/translocated in liposarcoma (FUS/TLS or FUS) is concentrated within cytoplasmic stress granules under conditions of induced stress. Since only the mutants, but not the endogenous wild-type FUS, are associated with stress granules under most of the stress conditions reported to date, the relationship between FUS and stress granules represents a mutant-specific phenotype and thus may be of significance in mutant-induced pathogenesis. While the association of mutant-FUS with stress granules is well established, the effect of the mutant protein on stress granules has not been examined. Here we investigated the effect of mutant-FUS on stress granule formation and dynamics under conditions of oxidative stress. Results We found that expression of mutant-FUS delays the assembly of stress granules. However, once stress granules containing mutant-FUS are formed, they are more dynamic, larger and more abundant compared to stress granules lacking FUS. Once stress is removed, stress granules disassemble more rapidly in cells expressing mutant-FUS. These effects directly correlate with the degree of mutant-FUS cytoplasmic localization, which is induced by mutations in the nuclear localization signal of the protein. We also determine that the RGG domains within FUS play a key role in its association to stress granules. While there has been speculation that arginine methylation within these RGG domains modulates the incorporation of FUS into stress granules, our results demonstrate that this post-translational modification is not involved. Conclusions Our results indicate that mutant-FUS alters the dynamic properties of stress granules, which is consistent with a gain-of-toxic mechanism for mutant-FUS in stress granule assembly and cellular stress response. PMID:24090136

  3. Comorbidity between post-traumatic stress disorder and major depressive disorder: alternative explanations and treatment considerations.

    PubMed

    Flory, Janine D; Yehuda, Rachel

    2015-06-01

    Approximately half of people with post-traumatic stress disorder (PTSD) also suffer from Major Depressive Disorder (MDD). The current paper examines evidence for two explanations of this comorbidity. First, that the comorbidity reflects overlapping symptoms in the two disorders. Second, that the co-occurrence of PTSD and MDD is not an artifact, but represents a trauma-related phenotype, possibly a subtype of PTSD. Support for the latter explanation is inferred from literature that examines risk and biological correlates of PTSD and MDD, including molecular processes. Treatment implications of the comorbidity are considered.

  4. Comorbidity between post-traumatic stress disorder and major depressive disorder: alternative explanations and treatment considerations

    PubMed Central

    Flory, Janine D.; Yehuda, Rachel

    2015-01-01

    Approximately half of people with post-traumatic stress disorder (PTSD) also suffer from Major Depressive Disorder (MDD). The current paper examines evidence for two explanations of this comorbidity. First, that the comorbidity reflects overlapping symptoms in the two disorders. Second, that the co-occurrence of PTSD and MDD is not an artifact, but represents a trauma-related phenotype, possibly a subtype of PTSD. Support for the latter explanation is inferred from literature that examines risk and biological correlates of PTSD and MDD, including molecular processes. Treatment implications of the comorbidity are considered. PMID:26246789

  5. Repeated ethanol exposure alters social behavior and oxidative stress parameters of zebrafish.

    PubMed

    Müller, Talise Ellwanger; Nunes, Stenio Zimermann; Silveira, Ariane; Loro, Vania Lucia; Rosemberg, Denis Broock

    2017-06-07

    Repeated ethanol (EtOH) consumption induces neurological disorders in humans and is considered an important public health problem. The physiological effects of EtOH are dose- and time-dependent, causing relevant changes in the social behavior. In addition, alcohol-induced oxidative stress has been proposed as a key mechanism involved in EtOH neurotoxicity. Here we investigate for the first time whether repeated EtOH exposure (REE) alters the social behavior of zebrafish and influences brain oxidation processes. Animals were exposed to water (control group) or 1% (v/v) EtOH (EtOH group) for 8 consecutive days (20min per day). EtOH was added directly to the tank water. At day 9, the social behavior and biochemical parameters were assessed. REE increased shoal cohesion by reducing inter-fish and farthest neighbor distances. SOD and CAT activities, as well as NPSH levels decreased in brain tissue. Moreover, REE increased lipid peroxidation suggesting oxidative damage. In summary, changes in oxidation processes may play a role in the CNS effects of EtOH, influencing the social behavior of zebrafish. Furthermore, in a translational neuroscience perspective, our data reinforces the utility of zebrafish to clarify the biochemical and behavioral effects of intermittent EtOH administration. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Oxidative stress and alterations in actin cytoskeleton trigger glutathione efflux in Saccharomyces cerevisiae.

    PubMed

    Bradamante, Silvia; Villa, Alessandro; Versari, Silvia; Barenghi, Livia; Orlandi, Ivan; Vai, Marina

    2010-12-01

    A marked deficiency in glutathione (GSH), the most abundant antioxidant in living systems, plays a major role in aging and the pathogenesis of diseases ranging from neurological disorders to early atherosclerosis and the impairment of various immunological functions. In an attempt to shed light on GSH homeostasis, we carried out the space experiment SCORE (Saccharomyces cerevisiae oxidative stress response evaluation) during the FOTON-M3 mission. Microgravity and hyperoxic conditions induced an enormous extracellular release of GSH from S. cerevisiae cells (≈40% w/dw), changed the distribution of the buds, and activated the high osmolarity glycerol (HOG) and cell integrity/PKC pathways, as well as protein carbonylation. The results from the single spaceflight experiment were validated by a complete set of experiments under conditions of simulated microgravity and indicate that cytoskeletal alterations are mainly responsible for the observed effects. The results of ground experiments in which we induced cytoskeletal modifications by means of treatment with dihydrocytochalasin B (DHCB), a potent inhibitor of actin polymerisation, or (R)-(+)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide dihydrochloride monohydrate (Y-27632), a selective ROCK (Rho-associated coiled-coil forming protein serine/threonine kinase) inhibitor, confirmed the role of actin in GSH efflux. We also found that the GSH release can be inhibited using the potent chloride channel blocker 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB).

  7. Exposure to chronic pregnancy stress reverses peripartum-associated adaptations: implications for postpartum anxiety and mood disorders.

    PubMed

    Hillerer, Katharina M; Reber, Stefan O; Neumann, Inga D; Slattery, David A

    2011-10-01

    Maternal adaptations, such as decreased anxiety and attenuated stress responsiveness, are necessary to enable successful postnatal development of the offspring. However, there is growing evidence that they are also required to protect the mental health of the mother and that exposure to chronic stress during pregnancy may prevent such adaptations. Overcrowding stress (24 h) and restraint stress (2 × 1 h) were employed on alternate days between pregnancy d 4-16 to examine the impact of chronic pregnancy stress on relevant behavioral, neuroendocrine, and neuronal peripartum adaptations. To determine whether the chronic stress-induced alterations were specific to the peripartum period, we included virgins as controls. Validating the stress procedure, we demonstrated decreased body-weight gain and increased adrenal weight in stressed dams, relative to their nonstressed controls. Chronic stress prevented a number of peripartum adaptations, including basal plasma hypercorticosterone levels, increased oxytocin mRNA expression in the hypothalamic paraventricular nucleus, and anxiolysis. However, chronic stress did not prevent the peripartum-associated decrease in CRH mRNA expression or attenuate corticosterone response to an acute stressor, nor did it affect hypothalamic vasopressin mRNA expression. Illustrating the specificity of these stress-induced changes to the peripartum period, none of these parameters were affected in stressed virgins. Although chronic stress did not alter depression-related behavior, it reversed the response to acute imipramine treatment and increased active maternal behavior in lactation. Thus, prevention of the peripartum-associated increases in basal corticosterone and oxytocin system activity by pregnancy stress reveal two alterations that may increase the risk of postpartum psychiatric disorders, particularly anxiety.

  8. Prenatal Alcohol Exposure and Chronic Mild Stress Differentially Alter Depressive- and Anxiety-Like Behaviors in Male and Female Offspring

    PubMed Central

    Hellemans, Kim G. C.; Verma, Pamela; Yoon, Esther; Yu, Wayne K.; Young, Allan H.; Weinberg, Joanne

    2016-01-01

    Background Fetal Alcohol Spectrum Disorder (FASD) is associated with numerous neuro behavioral alterations, as well as disabilities in a number of domains, including a high incidence of depression and anxiety disorders. Prenatal alcohol exposure (PAE) also alters hypothalamic-pituitary-adrenal (HPA) function, resulting in increased responsiveness to stressors and HPA dysregulation in adulthood. Interestingly, data suggest that pre-existing HPA abnormalities may be a major contributory factor to some forms of depression, particularly when an individual is exposed to stressors later in life. We tested the hypothesis that exposure to stressors in adulthood may unmask an increased vulnerability to depressive- and anxiety-like behaviors in PAE animals. Methods Male and female offspring from prenatal alcohol (PAE), pair-fed (PF), and ad libitumfed control (C) treatment groups were tested in adulthood. Animals were exposed to 10 consecutive days of chronic mild stress (CMS), and assessed in a battery of well-validated tasks sensitive to differences in depressive- and / or anxiety-like behaviors. Results We report here that the combination of PAE and CMS in adulthood increases depressive- and anxiety-like behaviors in a sexually dimorphic manner. PAE males showed impaired hedonic responsivity (sucrose contrast test), locomotor hyperactivity (open field), and alterations in affiliative and nonaffiliative social behaviors (social interaction test) compared to control males. By contrast, PAE and, to a lesser extent, PF, females showed greater levels of “behavioral despair” in the forced swim test, and PAE females showed altered behavior in the final 5 minutes of the social interaction test compared to control females. Conclusions These data support the possibility that stress may be a mediating or contributing factor in the psychopathologies reported in FASD populations. PMID:20102562

  9. Alterations of GABAergic signaling in autism spectrum disorders.

    PubMed

    Pizzarelli, Rocco; Cherubini, Enrico

    2011-01-01

    Autism spectrum disorders (ASDs) comprise a heterogeneous group of pathological conditions, mainly of genetic origin, characterized by stereotyped behavior, marked impairment in verbal and nonverbal communication, social skills, and cognition. Interestingly, in a small number of cases, ASDs are associated with single mutations in genes encoding for neuroligin-neurexin families. These are adhesion molecules which, by regulating transsynaptic signaling, contribute to maintain a proper excitatory/inhibitory (E/I) balance at the network level. Furthermore, GABA, the main inhibitory neurotransmitter in adult life, at late embryonic/early postnatal stages has been shown to depolarize and excite targeted cell through an outwardly directed flux of chloride. The depolarizing action of GABA and associated calcium influx regulate a variety of developmental processes from cell migration and differentiation to synapse formation. Here, we summarize recent data concerning the functional role of GABA in building up and refining neuronal circuits early in development and the molecular mechanisms regulating the E/I balance. A dysfunction of the GABAergic signaling early in development leads to a severe E/I unbalance in neuronal circuits, a condition that may account for some of the behavioral deficits observed in ASD patients.

  10. Altered fecal microbiota composition in patients with major depressive disorder.

    PubMed

    Jiang, Haiyin; Ling, Zongxin; Zhang, Yonghua; Mao, Hongjin; Ma, Zhanping; Yin, Yan; Wang, Weihong; Tang, Wenxin; Tan, Zhonglin; Shi, Jianfei; Li, Lanjuan; Ruan, Bing

    2015-08-01

    Studies using animal models have shown that depression affects the stability of the microbiota, but the actual structure and composition in patients with major depressive disorder (MDD) are not well understood. Here, we analyzed fecal samples from 46 patients with depression (29 active-MDD and 17 responded-MDD) and 30 healthy controls (HCs). High-throughput pyrosequencing showed that, according to the Shannon index, increased fecal bacterial α-diversity was found in the active-MDD (A-MDD) vs. the HC group but not in the responded-MDD (R-MDD) vs. the HC group. Bacteroidetes, Proteobacteria, and Actinobacteria strongly increased in level, whereas that of Firmicutes was significantly reduced in the A-MDD and R-MDD groups compared with the HC group. Despite profound interindividual variability, levels of several predominant genera were significantly different between the MDD and HC groups. Most notably, the MDD groups had increased levels of Enterobacteriaceae and Alistipes but reduced levels of Faecalibacterium. A negative correlation was observed between Faecalibacterium and the severity of depressive symptoms. These findings enable a better understanding of changes in the fecal microbiota composition in such patients, showing either a predominance of some potentially harmful bacterial groups or a reduction in beneficial bacterial genera. Further studies are warranted to elucidate the temporal and causal relationships between gut microbiota and depression and to evaluate the suitability of the microbiome as a biomarker. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Alterations of GABAergic Signaling in Autism Spectrum Disorders

    PubMed Central

    Pizzarelli, Rocco; Cherubini, Enrico

    2011-01-01

    Autism spectrum disorders (ASDs) comprise a heterogeneous group of pathological conditions, mainly of genetic origin, characterized by stereotyped behavior, marked impairment in verbal and nonverbal communication, social skills, and cognition. Interestingly, in a small number of cases, ASDs are associated with single mutations in genes encoding for neuroligin-neurexin families. These are adhesion molecules which, by regulating transsynaptic signaling, contribute to maintain a proper excitatory/inhibitory (E/I) balance at the network level. Furthermore, GABA, the main inhibitory neurotransmitter in adult life, at late embryonic/early postnatal stages has been shown to depolarize and excite targeted cell through an outwardly directed flux of chloride. The depolarizing action of GABA and associated calcium influx regulate a variety of developmental processes from cell migration and differentiation to synapse formation. Here, we summarize recent data concerning the functional role of GABA in building up and refining neuronal circuits early in development and the molecular mechanisms regulating the E/I balance. A dysfunction of the GABAergic signaling early in development leads to a severe E/I unbalance in neuronal circuits, a condition that may account for some of the behavioral deficits observed in ASD patients. PMID:21766041

  12. Altered salience processing in attention deficit hyperactivity disorder

    PubMed Central

    Tegelbeckers, Jana; Bunzeck, Nico; Duzel, Emrah; Bonath, Björn; Flechtner, Hans-Henning; Krauel, Kerstin

    2015-01-01

    Attentional problems in patients with attention deficit hyperactivity disorder (ADHD) have often been linked with deficits in cognitive control. Whether these deficits are associated with increased sensitivity to external salient stimuli remains unclear. To address this issue, we acquired functional brain images (fMRI) in 38 boys with and without ADHD (age: 11–16 years). To differentiate the effects of item novelty, contextual rareness and task relevance, participants performed a visual oddball task including four stimulus categories: a frequent standard picture (62.5%), unique novel pictures (12.5%), one repeated rare picture (12.5%), and a target picture (12.5%) that required a specific motor response. As a main finding, we can show considerable overlap in novelty-related BOLD responses between both groups, but only healthy participants showed neural deactivation in temporal as well as frontal regions in response to novel pictures. Furthermore, only ADHD patients, but not healthy controls, engaged wide parts of the novelty network when processing the rare but familiar picture. Our results provide first evidence that ADHD patients show enhanced neural activity in response to novel but behaviorally irrelevant stimuli as well as reduced habituation to familiar items. These findings suggest an inefficient use of neuronal resources in children with ADHD that could be closely linked to increased distractibility. Hum Brain Mapp 36:2049–2060, 2015. © 2015 Wiley Periodicals, Inc. PMID:25648705

  13. Altered mu-rhythm suppression in Borderline Personality Disorder.

    PubMed

    Martin, Franziska; Flasbeck, Vera; Brown, Elliot C; Brüne, Martin

    2017-03-15

    Borderline Personality Disorder (BPD) is characterized, among other symptoms, by interpersonal dysfunction and difficulties in empathizing. According to Simulation Theory empathy is linked to the activity of the mirror neuron system (MNS). Mu-rhythm desynchronization, as reflected in a suppression of electroencephalographic alpha-frequency bands (8-13Hz) provides a non-invasive electrophysiological window into MNS function. Here, we analyzed mu-desynchronization in twenty-two patients with BPD and twenty-three matched healthy controls in a reward and punishment-sensitive action observation task. In addition, we examined empathy using the Interpersonal Reactivity Index. BPD patients and controls did not differ with regard to mu-desynchronization when the entire time course was compared. However, differences in mu-suppression between groups occurred after the goal of the action became discernible. Correlations between mu-suppression and empathy ratings emerged only in controls, but not in the patient group. These findings suggest that BPD patients do not have a generalized impairment in MNS activity, though associations with contextual factors seem plausible.

  14. Masticatory performance alters stress relief effect of gum chewing.

    PubMed

    Nishigawa, Keisuke; Suzuki, Yoshitaka; Matsuka, Yoshizo

    2015-10-01

    We evaluated the effects of gum chewing on the response to psychological stress induced by a calculation task and investigated the relationship between this response and masticatory performance. Nineteen healthy adult volunteers without dental problems undertook the Uchida-Kraepelin (UK) test (30 min of reiterating additions of one-digit numbers). Before and immediately after the test, saliva samples were collected from the sublingual area of the participants. Three min after the UK test, the participants were made to chew flavorless gum for 3 min, and the final saliva samples were collected 10 min after the UK test. The experiment was performed without gum chewing on a different day. Masticatory performance was evaluated using color-changing chewing gum. Salivary CgA levels at immediately and 10 min after the UK test were compared with and without gum chewing condition. Two-way repeated measures analysis of variance revealed significant interaction between gum chewing condition and changes in CgA levels during post 10 min UK test period. A significant correlation was found between changes in CgA levels and masticatory performance in all participants. Our results indicate that gum chewing may relieve stress responses; however, high masticatory performance is required to achieve this effect. Copyright © 2015 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

  15. Posttraumatic stress disorder is associated with emotional eating.

    PubMed

    Talbot, Lisa S; Maguen, Shira; Epel, Elissa S; Metzler, Thomas J; Neylan, Thomas C

    2013-08-01

    The present study investigated the relationship between posttraumatic stress disorder (PTSD) and emotional eating in a sample of medically healthy and medication-free adults. Participants with PTSD (n = 44) and control participants free of lifetime psychiatric history (n = 49) completed a measure of emotional eating. Emotional eating is the tendency to eat or overeat in response to negative emotions. PTSD participants exhibited greater emotional eating than control participants (η(2)  = .20) and emotional eating increased with higher PTSD symptom severity (R(2)  = .11). Results supported the stress-eating-obesity model whereby emotional eating is a maladaptive response to stressors. Over time, this could lead to weight gain, particularly abdominal stores, and contribute to higher risk for comorbid medical disorders. Findings suggest the importance of future longitudinal research to understand whether emotional eating contributes to the high rates of obesity, diabetes, and heart disease in PTSD.

  16. Brain function and conditioning in posttraumatic stress disorder.

    PubMed

    Redgrave, K

    2003-06-01

    Posttraumatic stress disorder (PTSD) is commonly treated by psychotherapy, which may draw upon behavioural psychology or cognitive-behavioural psychology, thereby making use of desensitisation techniques--amongst others; hypnotherapy may also be used. Hypnotherapy and psychotherapy are also available for helping patients who suffer from symptoms associated with general stress or who show phobic symptoms, such as a fear of heights or of walking across bridges. Studies of patients with such disorders have not always linked emotional (affective) and behavioural symptoms with psychophysical factors, which correlate with the symptoms. The present article not only does this, but also shows that it is possible for brain function and psychoemotional outcome to mislead a person and 'trick' him or her into believing that certain fears or panics appear 'out of the blue' or might be due to experiences other than the true cause. These may be important when, for instance, childhood memories form an issue in any court case.

  17. Aroused at Home: Basic Autonomic Regulation during Orthostatic and Physical Activation is Altered in Children with Social Anxiety Disorder.

    PubMed

    Asbrand, Julia; Blechert, Jens; Nitschke, Kai; Tuschen-Caffier, Brunna; Schmitz, Julian

    2017-01-01

    Previous research has documented altered autonomic nervous system (ANS) reactivity to laboratory-based social stress tasks in children with social anxiety disorder (SAD). It is unclear, however, whether these alterations are caused by the unfamiliar and possibly threatening lab environment or whether they generalize to other, more representative contexts. Sympathetic and parasympathetic autonomic functioning was assessed in the home (minimizing environmental threat) during a supine baseline phase and two physical activation phases (orthostatic stress, stair stepping) in children (9-13 years) with SAD (n = 27) and healthy control children (n = 27). Relative to controls, children with SAD showed tonic autonomic hyperarousal as indicated by higher heart rate and electrodermal activity during the supine baseline phase. Further, there was evidence for stronger cardiac and vascular sympathetic reactivity (T-wave amplitude, pulse wave transit time) to moderate physical activation in children with SAD. Higher autonomic arousal during rest was related to measures of trait social anxiety and general psychopathology. Groups did not differ on parasympathetic parameters. Our results extend previous laboratory findings and provide the first evidence for alterations in children with SAD during basal autonomic regulation and in the absence of explicit social evaluative threat. They may further help to clarify conflicting study results from previous laboratory studies. The findings underline the importance of psychophysiological assessment using different environments and tasks to elucidate the physiological bases of SAD.

  18. Changing the Air Force Disqualification Policy for Post-Traumatic Stress Disorder and Other Trauma-Related Disorders

    DTIC Science & Technology

    2015-07-21

    Mental Disorders, 5th Edition ( DSM -5), a PTSD diagnosis requires exposure to one or more traumatic events where actual or threatened death, serious...recommendation). ACS clinical records were searched for DSM -5 trauma- and stressor-related disorders, * U.S...ACRONYMS ACS Aeromedical Consultation Service ASD acute stress disorder DNIF duty not including flying DSM -5 Statistical Manual of Mental Disorders

  19. Examining the relationship between post-traumatic stress disorder and social participation among Veterans with spinal cord injuries and disorders.

    PubMed

    Etingen, Bella; Locatelli, Sara M; Miskevics, Scott; LaVela, Sherri L

    2017-07-26

    The objectives of this study were to examine differences in social participation among Veterans with spinal cord injuries/disorders with and without post-traumatic s