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Sample records for stress disorder alterations

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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.

  13. 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

  14. Posttraumatic Stress Disorder

    MedlinePlus

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  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. Posttraumatic Stress Disorder

    MedlinePlus

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  1. 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.

  2. Post-traumatic stress disorder

    MedlinePlus

    ... medlineplus.gov/ency/article/000925.htm Post-traumatic stress disorder To use the sharing features on this page, please enable JavaScript. Post-traumatic stress disorder (PTSD) is a type of anxiety disorder . ...

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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)

  9. 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

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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

  16. Posttraumatic Stress Disorder

    MedlinePlus

    ... stressful events or learn about an unexpected or violent death or injury to a family member or ... should. Traumatic events that can cause PTSD include: violent assaults, including rape fire physical or sexual abuse ...

  17. 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.

  18. Postpartum Post-Traumatic Stress Disorder

    MedlinePlus

    ... Depression During Pregnancy & Postpartum Anxiety During Pregnancy & Postpartum Pregnancy or Postpartum Obsessive Symptoms Postpartum Post-Traumatic Stress Disorder Bipolar Mood Disorders Postpartum Psychosis Tools for ...

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  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. 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.

  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. 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

  8. [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.

  9. 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.

  10. 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, ...

  11. 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.

  12. 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.

  13. 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.

  14. 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…

  15. 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.

  16. 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.

  17. 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.

  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. 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.

  1. 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

  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. 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

  4. What is post-traumatic stress disorder?

    PubMed Central

    Andreasen, Nancy C.

    2011-01-01

    Although post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI) are categorized as separate and discrete disorders, the boundary between them is sometimes indistinct. Their separation is based on the assumption that PTSD results primarily from psychological stress, while TBI is the consequence of an identifiable injury to the brain. This distinction is based on an antiquated polarity between mind and brain, and the separation of the two disorders often becomes arbitrary in day-to-day psychiatric practice and research. PMID:22033951

  5. 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

  6. 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.

  7. 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…

  8. 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…

  9. 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 =…

  10. 75 FR 39843 - Stressor Determinations for Posttraumatic Stress Disorder

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-13

    ... AFFAIRS 38 CFR Part 3 RIN 2900-AN32 Stressor Determinations for Posttraumatic Stress Disorder AGENCY... amending its adjudication regulations governing service connection for posttraumatic stress disorder (PTSD... & Health, Vol. 6: Physiologic, Psychologic, and Psychosocial Effects of Deployment- Related Stress,...

  11. Mortuary Affairs Soldiers: Early Intervention and Altering Barriers to Care for Traumatic Stress and PTSD

    DTIC Science & Technology

    2013-09-01

    to Care for Traumatic Stress and PTSD PRINCIPAL INVESTIGATOR: Carol S. Fullerton, Ph.D. CONTRACTING ORGANIZATION: The Henry M...Intervention and Altering Barriers to Care for Traumatic Stress and PTSD 5b. GRANT NUMBER W81XWH-08-2-0180 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...care for MA Soldiers and 2) assessing the effectiveness of TEAM on disorder (e.g., PTSD , depression), distress, health risk behaviors (e.g., alcohol or

  12. 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…

  13. 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

  14. 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

  15. 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

  16. 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.

  17. 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)

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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…

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. Post traumatic stress disorder in anorexia nervosa

    PubMed Central

    Reyes-Rodríguez, Mae Lynn; Von Holle, Ann; Ulman, T. Frances; Thornton, Laura M.; Klump, Kelly L.; Brandt, Harry; Crawford, Steve; Fichter, Manfred M.; Halmi, Katherine A.; Huber, Thomas; Johnson, Craig; Jones, Ian; Kaplan, Allan S.; Mitchell, James E.; Strober, Michael; Treasure, Janet; Woodside, D. Blake; Berrettini, Wade H.; Kaye, Walter H.; Bulik, Cynthia M.

    2011-01-01

    Objective Comorbidity among eating disorders, traumatic events, and post traumatic stress disorder (PTSD) has been reported in several studies. The main objectives of this study were to describe the nature of traumatic events experienced and to explore the relation between PTSD and anorexia nervosa (AN) in a sample of women. Methods Eight hundred twenty-four participants from the National Institutes of Health funded Genetics of Anorexia Nervosa Collaborative Study were assessed for eating disorders, PTSD, and personality characteristics. Results From a final sample of 753 women with AN, 13.7% (n=103) met DSM-IV criteria for PTSD. The sample mean age was 29.5 years (SD=11.1). In pairwise comparisons across AN subtypes, the odds of having a PTSD diagnosis were significantly lower in individuals with restricting AN (RAN) than individuals with purging AN without binge eating (PAN) (OR=0.49, 95% CI=0.30, 0.80). The majority of participants with PTSD reported the first traumatic event before the onset of AN (64.1%, n=66). The most common traumatic events reported by those with a PTSD diagnosis were sexual related traumas during childhood (40.8%) and during adulthood (35.0%). Conclusions AN and PTSD do co-occur and traumatic events tend to occur prior to the onset of AN. Clinically, these results underscore the importance of assessing trauma history and PTSD in individuals with AN and raise the question of whether specific modifications or augmentations to standard treatment for AN should be considered in a subgroup to address PTSD-related psychopathology. PMID:21715295

  10. 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

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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…

  19. 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.

  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. 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

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Altered brain network modules induce helplessness in major depressive disorder

    PubMed Central

    Peng, Daihui; Shi, Feng; Shen, Ting; Peng, Ziwen; Zhang, Chen; Liu, Xiaohua; Qiu, Meihui; Liu, Jun; Jiang, Kaida; Shen, Dinggang

    2017-01-01

    Objective The abnormal brain functional connectivity (FC) has been assumed to be a pathophysiological aspect of major depressive disorder (MDD). However, it is poorly understood, regarding the underlying patterns of global FC network and their relationships with the clinical characteristics of MDD. Methods Resting-state functional magnetic resonance imaging data were acquired from 16 first episode, medication-naïve MDD patients and 16 healthy control subjects. The global FC network was constructed using 90 brain regions. The global topological patterns, e.g., small-worldness and modularity, and their relationships with depressive characteristics were investigated. Furthermore, the participant coefficient and module degree of MDD patients were measured to reflect the regional roles in module network, and the impairment of FC was examined by network based statistic. Results Small-world property was not altered in MDD. However, MDD patients exhibited 5 atypically reorganized modules compared to the controls. A positive relationship was also found among MDD patients between the intra-module I and helplessness factor evaluated via the Hamilton Depression Scale. Specifically, eight regions exhibited the abnormal participant coefficient or module degree, e.g., left superior orbital frontal cortex and right amygdala. The decreased FC was identified among the sub-network of 24 brain regions, e.g., frontal cortex, supplementary motor area, amygdala, thalamus, and hippocampus. Limitation The limited size of MDD samples precluded meaningful study of distinct clinical characteristics in relation to aberrant FC. Conclusions The results revealed altered patterns of brain module network at the global level in MDD patients, which might contribute to the feelings of helplessness. PMID:25033474

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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…

  17. 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.

  18. 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

  19. 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)

  20. 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.

  1. 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

  2. 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…

  3. 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…

  4. 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

  5. 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…

  6. 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

  7. [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.

  8. 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…

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. Sleep and Posttraumatic Stress Disorder (PTSD)

    MedlinePlus

    ... Z) Hepatitis HIV Mental Health Mental Health Home Suicide Prevention Substance Abuse Military Sexual Trauma PTSD Research ( ... PTSD Coach Online Tools to help you manage stress. Search Pilots Search PILOTS *, the largest citation database ...

  1. 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 ...

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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…

  11. 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…

  12. 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…

  13. 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…

  14. [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.

  15. 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

  16. 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…

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 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

  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. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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…

  12. 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.…

  13. 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.…

  14. 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)…

  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. 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)

  17. 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)

  18. 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...

  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. 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…

  1. 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

  2. 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…

  3. 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.

  4. 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…

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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.

  13. Traumatic stress disorders following first-trimester spontaneous abortion.

    PubMed

    Bowles, Stephen V; Bernard, Rebecca S; Epperly, Ted; Woodward, Stephanie; Ginzburg, Karni; Folen, Raymond; Perez, Theresita; Koopman, Cheryl

    2006-11-01

    Provide counsel and support to women after a spontaneous abortion. Research indicates that many women will talk with their physician about their emotional distress and that physicians provide good information after the spontaneous abortion. Evaluate women for acute stress disorder (ASD) after a spontaneous abortion. Research found that women reporting physical, emotional, or sexual abuse are more likely to experience ASD. Patients should be assessed for post-traumatic stress disorder in follow-up visits 1 month after the initial visit. Research has found that up to 25% of women meet criteria for PTSD 1 month post the spontaneous abortion and 7% met criteria at 4 months. Physicians should refer women who are experiencing traumatic stress to a behavioral health professional.

  14. 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.

  15. 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

  16. 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.

  17. [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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. 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'.

  5. 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.

  6. 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.

  7. Interplay of endoplasmic reticulum stress and autophagy in neurodegenerative disorders.

    PubMed

    Cai, Yu; Arikkath, Jyothi; Yang, Lu; Guo, Ming-Lei; Periyasamy, Palsamy; Buch, Shilpa

    2016-01-01

    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.

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. Mortuary Affairs Soldiers: Early Intervention and Altering Barriers to Care for Traumatic Stress and PTSD

    DTIC Science & Technology

    2012-09-01

    Therapy: CBT is an approach to altering thoughts and beliefs that lead to negative emotions. It has been shown to successfully treat and prevent PTSD ... CBT is an approach to altering thoughts and beliefs that lead to negative emotions. It has been shown to successfully treat and prevent PTSD ...Intervention and Altering Barriers to Care for Traumatic Stress and PTSD PRINCIPAL INVESTIGATOR: Carol S. Fullerton, Ph.D

  4. 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.

  5. 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.

  6. Latent Classes of Adolescent Posttraumatic Stress Disorder Predict Functioning and Disorder after 1 Year

    ERIC Educational Resources Information Center

    Ayer, Lynsay; Danielson, Carla Kmett; Amstadter, Ananda B.; Ruggiero, Ken; Saunders, Ben; Kilpatrick, Dean

    2011-01-01

    Objective: To identify latent classes of posttraumatic stress disorder (PTSD) symptoms in a national sample of adolescents, and to test their associations with PTSD and functional impairment 1 year later. Method: A total of 1,119 trauma-exposed youth aged 12 through 17 years (mean = 14.99 years, 51% female and 49% male) participating in the…

  7. Autism Spectrum Disorder and Fetal Alcohol Spectrum Disorder. Part II: A Qualitative Comparison of Parenting Stress

    ERIC Educational Resources Information Center

    Watson, Shelley L.; Hayes, Stephanie A.; Coons, Kelly D.; Radford-Paz, Elisa

    2013-01-01

    Background: Researchers investigating the impact of parenting children with disabilities suggest that regardless of the specific diagnosis, parents experience increased levels of stress. However, particular disabilities may be associated with distinct stressors and strains. Method: Parents of children with autism spectrum disorder (ASD) and…

  8. The MMPI-2 Restructured Clinical Scales in the Assessment of Posttraumatic Stress Disorder and Comorbid Disorders

    ERIC Educational Resources Information Center

    Wolf, Erika J.; Miller, Mark W.; Orazem, Robert J.; Weierich, Mariann R.; Castillo, Diane T.; Milford, Jaime; Kaloupek, Danny G.; Keane, Terence M.

    2008-01-01

    This study examined the psychometric properties of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) Restructured Clinical Scales (RCSs) in individuals with posttraumatic stress disorder (PTSD) receiving clinical services at Department of Veterans Affairs medical centers. Study 1 included 1,098 men who completed the MMPI-2 and were…

  9. 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

  10. 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.

  11. 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.

  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. 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.

  14. Stress and distress in non-organic voice disorder.

    PubMed

    Seifert, Eberhard; Kollbrunner, Juerg

    2005-07-09

    Non-organic voice disorders are characterised by an impaired voice sound, and/or reduced vocal capacity, and/or laryngeal sensory disturbances, all in the absence of causal organic laryngeal pathology. Psychogenic causes, a "psychological disequilibrium", and an increased tension of the laryngeal muscles are presumed to be one end of the spectrum of possible factors leading to the development of the disorder. In making a diagnosis, perceptive and acoustic methods for voice analysis are used in addition to the ENT-examination and the laryngostroboscopy. An assessment of the degree to which the patient feels him/herself subjectively affected by the voice disorder also plays an important role. If the history reveals any indication of psychosocial stress or conflict, the patient is offered psychological consultations. These conflicts seem less often to be deep rooted psychopathological problems but rather daily anxieties, failures, injuries, annoyances, disappointments regarding the sufferer him/herself and others, the non-fulfillment of desires, feelings of inadequacy and of lack of self-confidence. The patients may find it difficult to speak about conflicts and feelings, and they follow social conventions to an excessive extent. In frustrating situations patients tend to react aggressively towards themselves rather than towards others and are too quick in seeking a solution to any problem that may arise. The role of the voice as a "barometer of emotion", where a disorder may be regarded as a sign of emotional stress, has to be taken into consideration before starting a therapy: If the non-organic voice disorder is obviously due to vocal misuse and muscle tension, a more symptom-orientated voice therapy may be favoured. If psychosocial stress seems to play a greater role, additional counseling may be necessary. Only by using this approach can the patient be offered a therapy which goes into the causes and thereby addresses the whole person.

  15. 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.

  16. 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

  17. Posttraumatic stress disorder in early childhood: classification and diagnostic issues

    PubMed Central

    Simonelli, Alessandra

    2013-01-01

    The 0–3 diagnostic classification of infant mental health, on the basis of DSM-IV-R, describes posttraumatic stress disorder (PTSD) as a pattern of symptoms that may be shown by children who have experienced a single traumatic event, a series of connected traumatic events, or chronic, enduring stress situations. This definition, related to young children, needs the consideration of several factors to understand the child's symptoms, organize the diagnostic process, and realize clinical interventions. In this sense, the clinician must appreciate the classification criteria of PTSD in early childhood in the context of the child's age, temperament, and developmental level. This report presents a review of the research in the domain of the PTSD in early childhood with particular attention to the developmental considerations to define critical diagnostic criteria, specifically organized on the child characteristics, competences, and needs. Along this line, it will describe two proposed modifications of the diagnostic classification in childhood: the Post Traumatic Stress Disorder Alternative Algorithm (PTSD-AA) and the definition of developmental trauma disorder (DTD). PMID:24371512

  18. Pharmacological enhancement of behavioral therapy: focus on posttraumatic stress disorder.

    PubMed

    Choi, Dennis C; Rothbaum, Barbara O; Gerardi, Maryrose; Ressler, Kerry J

    2010-01-01

    Improved efficacy in the treatment of posttraumatic stress disorder (PTSD) and other anxiety disorders is urgently needed. Traditional anxiety treatments of hypnosis and psychodynamic therapy may be of some help, but uncontrolled studies lead to inconclusive results on the efficacy of these treatment techniques. There is a larger literature supporting the efficacy of cognitive-behavioral procedures with PTSD, including prolonged exposure therapy, eye movement desensitization and reprocessing, and anxiety management techniques. The cutting-edge technology of virtual reality-based exposure therapy for PTSD is particularly exciting. To further build on effective psychosocial treatments, current pharmacological augmentation approaches to emotional learning are being combined with psychotherapy. In particular, D-cycloserine, a partial NMDA agonist, has shown to be effective in facilitating the exposure/extinction therapy to improve the efficacy of treating anxiety disorders, and may guide the way for new pharmacological enhancements of behavioral therapy.

  19. 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.

  20. 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.

  1. [Update on epigenetic regulation in pathophysiologies of stress-induced psychiatric disorders].

    PubMed

    Miyagawa, Kazuya; Tsuji, Minoru; Fujimori, Kanji; Takeda, Hiroshi

    2010-08-01

    Recent research has demonstrated that complex 'epigenetic' mechanisms, which regulate gene transcription without altering the DNA code, could play a critical role in the pathophysiology of psychiatric disorders. The present review summarizes recent evidence for the existence of sustained epigenetic mechanisms of gene regulation in several psychiatric disorders such as depression, schizophrenia and Rett syndrome. The gene transcriptions of the key molecules such as brain-derived neurotrophic factor (BDNF) or Reelin that play a role in on psychiatric disorders are regulated with histone modification or DNA methylation. Furthermore, one potential mechanism whereby stress can disrupt prenatal and/or neonatal development is through epigenetics, because the key issue of epigenetics is its long-term influence. In addition, we also found in the recent research that the epigenetic mechanism of gene regulation, especially histonedeacetylase, in the brain may be involved in the development of emotional resistance to stress stimuli. A better understanding of epigenetic regulation might provide new therapeutic avenues for disorders such as depression, schizophrenia, Rett syndrome and neurodevelopmental diseases.

  2. 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

  3. Post-Typhoon Prevalence of Post-traumatic Stress Disorder, Major Depressive Disorder, Panic Disorder and Generalized Anxiety Disorder in a Vietnamese Sample

    PubMed Central

    Amstadter, Ananda B.; Acierno, Ron; Richardson, Lisa; Kilpatrick, Dean G.; Gros, Daniel F.; Gaboury, Mario T.; Tran, Trinh Luong; Trung, Lam Tu; Tam, Nguyen Thanh; Tuan, Tran; Buoi, La Thi; Ha, Tran Thu; Thach, Tran Duc; Galea, Sandro

    2009-01-01

    In 2006, typhoon Xangsane disrupted a multi-agency health needs study of 4,982 individuals in Vietnam. Following this disaster, 798 of the original participants were re-interviewed to determine prevalence and risk-factors associated with post-traumatic stress disorder (PTSD), major depressive disorder (MDD), panic disorder (PD), and generalized anxiety disorder (GAD) according to the DSM-IV (APA, 1994). Post-typhoon prevalences were: PTSD 2.6%; MDD 5.9%; PD 9.3%; GAD 2.2%. Of those meeting criteria for a disorder, 70% reported only one disorder, 15% had two, 14% had three, and 1% met criteria for all four disorders. Risk factors for post-typhoon psychopathology differed among disorders, but generally were related to high typhoon exposure, prior trauma exposure, and in contrast to Western populations, higher age, but not gender. PMID:19455707

  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. Genetic Differences in the Immediate Transcriptome Response to Stress Predict Risk-Related Brain Function and Psychiatric Disorders.

    PubMed

    Arloth, Janine; Bogdan, Ryan; Weber, Peter; Frishman, Goar; Menke, Andreas; Wagner, Klaus V; Balsevich, Georgia; Schmidt, Mathias V; Karbalai, Nazanin; Czamara, Darina; Altmann, Andre; Trümbach, Dietrich; Wurst, Wolfgang; Mehta, Divya; Uhr, Manfred; Klengel, Torsten; Erhardt, Angelika; Carey, Caitlin E; Conley, Emily Drabant; Ruepp, Andreas; Müller-Myhsok, Bertram; Hariri, Ahmad R; Binder, Elisabeth B

    2015-06-03

    Depression risk is exacerbated by genetic factors and stress exposure; however, the biological mechanisms through which these factors interact to confer depression risk are poorly understood. One putative biological mechanism implicates variability in the ability of cortisol, released in response to stress, to trigger a cascade of adaptive genomic and non-genomic processes through glucocorticoid receptor (GR) activation. Here, we demonstrate that common genetic variants in long-range enhancer elements modulate the immediate transcriptional response to GR activation in human blood cells. These functional genetic variants increase risk for depression and co-heritable psychiatric disorders. Moreover, these risk variants are associated with inappropriate amygdala reactivity, a transdiagnostic psychiatric endophenotype and an important stress hormone response trigger. Network modeling and animal experiments suggest that these genetic differences in GR-induced transcriptional activation may mediate the risk for depression and other psychiatric disorders by altering a network of functionally related stress-sensitive genes in blood and brain.

  6. Glucocorticoid Mechanisms of Functional Connectivity Changes in Stress-Related Neuropsychiatric Disorders.

    PubMed

    Hall, Baila S; Moda, Rachel N; Liston, Conor

    2015-01-01

    Stress-especially chronic, uncontrollable stress-is an important risk factor for many neuropsychiatric disorders. The underlying mechanisms are complex and multifactorial, but they involve correlated changes in structural and functional measures of neuronal connectivity within cortical microcircuits and across neuroanatomically distributed brain networks. Here, we review evidence from animal models and human neuroimaging studies implicating stress-associated changes in functional connectivity in the pathogenesis of PTSD, depression, and other neuropsychiatric conditions. Changes in fMRI measures of corticocortical connectivity across distributed networks may be caused by specific structural alterations that have been observed in the prefrontal cortex, hippocampus, and other vulnerable brain regions. These effects are mediated in part by glucocorticoids, which are released from the adrenal gland in response to a stressor and also oscillate in synchrony with diurnal rhythms. Recent work indicates that circadian glucocorticoid oscillations act to balance synapse formation and pruning after learning and during development, and chronic stress disrupts this balance. We conclude by considering how disrupted glucocorticoid oscillations may contribute to the pathophysiology of depression and PTSD in vulnerable individuals, and how circadian rhythm disturbances may affect non-psychiatric populations, including frequent travelers, shift workers, and patients undergoing treatment for autoimmune disorders.

  7. The stress-vulnerability hypothesis in psychotic disorders: focus on the stress response systems.

    PubMed

    Gispen-de Wied, Christine C; Jansen, Lucres M C

    2002-06-01

    The vulnerabilty stress model is an intriguing concept to look into the etiology of psychotic disorders and, in particular, into the "nature nurture" principle. That stress affects a vulnerable nature may be obvious, but its mechanism is not well understood, and many questions remain to be answered, let alone how to define "vulnerability". The present review tries to focus on the core issues of the vulnerability stress concept--identifying vulnerability, the way stress interferes with it, and the possiblilities of modulating their interaction. Attention is drawn to the biologic stress response systems, the autonomic nervous system (ANS), the hypothalamic pituitary adrenal (HPA) system, and the immune system, and highlights the plasticity of the HPA system as the mediator of adaptation.

  8. 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

  9. Influences of Comorbid Disorders on Personality Assessment Inventory Profiles in Women with Posttraumatic Stress Disorder

    PubMed Central

    Drury, Pamela; Calhoun, Patrick S.; Boggs, Christina; Araujo, Gustavo; Dennis, Michelle F.; Beckham, Jean C.

    2011-01-01

    The present study describes Personality Assessment Inventory (PAI) profiles for women with posttraumatic stress disorder (PTSD). Four groups of women were sampled: single Axis I diagnosis of PTSD; PTSD and major depressive disorder (MDD); PTSD, MDD, at least one other Axis I disorder; and controls with no Axis I disorder. Higher comorbidity rates were associated with higher mean profile elevations and broader range of endorsed symptoms. The group with the highest rate of comorbidity produced profiles most similar to previously published reports of patients with PTSD. This is in contrast to women with a single diagnosis of PTSD, who produced relative mean elevations only on subscales measuring distress caused by trauma and physiological symptoms of depression. Thus, published profiles may be more reflective of PTSD with comorbidity than a single diagnosis of PTSD. PMID:21437198

  10. Panicogens in patients with Post-Traumatic Stress Disorder (PTSD).

    PubMed

    Muhtz, Christoph; Wiedemann, Klaus; Kellner, Michael

    2012-01-01

    Symptom provocation has proved its worth for understanding the pathophysiology of diseases and in general for the development of new therapeutic approaches in the medical field. In the research of anxiety disorders, investigations using experimentally induced panic attacks by various agents, such as sodium lactate, carbon dioxide, cholezystokinine-tetrapetid etc., have a long tradition and allow the exploration of usually naturally occuring spontaneous psychopathological phenomena under controlled conditions. Post-Traumatic Stress Disorder (PTSD) is a prevalent disorder that can develop following exposure to an extreme traumatic event. In DSM-IV it is currently classified as an anxiety disorder and shares phenomenological similarities with panic disorder. The use of panicogenic challenge tests is also an interesting neurobiological approach to learn more about the nature of PTSD and may be a possibility to develop new therapeutic strategies for the treatment of PTSD symptoms. Not only panic anxiety, but also flashbacks and other dissociative symptoms can be provoked by several panicogens in PTSD. The purpose of this review is to evaluate studies using panicogens in PTSD. Methodological short-comings of current studies and needed directions of further research are discussed.

  11. Posttraumatic stress disorder and the nature of trauma

    PubMed Central

    van der Kolk, Bessel

    2000-01-01

    The role of psychological trauma (eg, rape, physical assaults, torture, motor vehicle accidents) as an etiological factor in mental disorders, anticipated as early as the 19th century by Janet, Freud, and Breuer, and more specifically during World War I and II by Kardiner, was “rediscovered” some 20 years ago in the wake of the psychological traumas inflicted by the Vietnam war and the discussion “in the open ” of sexual abuse and rape by the women's liberation movement, 1980 marked a major turning point, with the incorporation of the diagnostic construct of posttraumatic stress disorder (PTSD) into the 3rd edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) and the definition of its main diagnostic criteria (reexperiencing of the traumatic event, avoidance of stimuli associated with the trauma, and symptoms of increased arousal). Initially described as resulting from a onetime severe traumatic incident, PTSD has now been shown to be triggered by chronic multiple traumas as well. This “state-of-the-art” article discusses past and current understanding of the disorder, with particular emphasis on the recent explosive developments in neuroimaging and other fields of the neurosciences that have highlighted the complex interrelationships between the psychological, psychiatric, biological, and neuroanatomical components of the disorder, and opened up entirely new therapeutic perspectives on how to help the victims of trauma overcome their past. PMID:22034447

  12. Posttraumatic Stress Disorder: A Theoretical Model of the Hyperarousal Subtype

    PubMed Central

    Weston, Charles Stewart E.

    2014-01-01

    Posttraumatic stress disorder (PTSD) is a frequent and distressing mental disorder, about which much remains to be learned. It is a heterogeneous disorder; the hyperarousal subtype (about 70% of occurrences and simply termed PTSD in this paper) is the topic of this article, but the dissociative subtype (about 30% of occurrences and likely involving quite different brain mechanisms) is outside its scope. A theoretical model is presented that integrates neuroscience data on diverse brain regions known to be involved in PTSD, and extensive psychiatric findings on the disorder. Specifically, the amygdala is a multifunctional brain region that is crucial to PTSD, and processes peritraumatic hyperarousal on grounded cognition principles to produce hyperarousal symptoms. Amygdala activity also modulates hippocampal function, which is supported by a large body of evidence, and likewise amygdala activity modulates several brainstem regions, visual cortex, rostral anterior cingulate cortex (rACC), and medial orbitofrontal cortex (mOFC), to produce diverse startle, visual, memory, numbing, anger, and recklessness symptoms. Additional brain regions process other aspects of peritraumatic responses to produce further symptoms. These contentions are supported by neuroimaging, neuropsychological, neuroanatomical, physiological, cognitive, and behavioral evidence. Collectively, the model offers an account of how responses at the time of trauma are transformed into an extensive array of the 20 PTSD symptoms that are specified in the Diagnostic and Statistical Manual of Mental Disorders, Fifth edition. It elucidates the neural mechanisms of a specific form of psychopathology, and accords with the Research Domain Criteria framework. PMID:24772094

  13. Neurofeedback Treatment and Posttraumatic Stress Disorder: Effectiveness of Neurofeedback on Posttraumatic Stress Disorder and the Optimal Choice of Protocol.

    PubMed

    Reiter, Karen; Andersen, Søren Bo; Carlsson, Jessica

    2016-02-01

    Neurofeedback is an alternative, noninvasive approach used in the treatment of a wide range of neuropsychiatric disorders, including posttraumatic stress disorder (PTSD). Many different neurofeedback protocols and methods exist. Likewise, PTSD is a heterogeneous disorder. To review the evidence on effectiveness and preferred protocol when using neurofeedback treatment on PTSD, a systematic search of PubMed, PsychInfo, Embase, and Cochrane databases was undertaken. Five studies were included in this review. Neurofeedback had a statistically significant effect in three studies. Neurobiological changes were reported in three studies. Interpretation of results is, however, limited by differences between the studies and several issues regarding design. The optimistic results presented here qualify neurofeedback as probably efficacious for PTSD treatment.

  14. Post-traumatic stress disorder and quality of life in sexually abused Australian children.

    PubMed

    Gospodarevskaya, Elena

    2013-01-01

    The study used publicly available data on post-traumatic stress disorder in a sample of the Australian population with a history of sexual abuse to demonstrate how this evidence can inform economic analyses. The 2007 Australian Mental Health Survey revealed that 8.3% of 993 adolescents experienced childhood sexual abuse, of which 40.2% were diagnosed with post-traumatic stress disorder. Post-traumatic stress disorder diagnosis corresponded to a significant loss of quality of life. Survival analysis was used to estimate the lifetime persistence of post-traumatic stress disorder symptoms. The average time between post-traumatic stress disorder onset and remission was 11.4 years. Results suggest that successful treatment of post-traumatic stress disorder will save 2.05 quality adjusted life years per child or adolescent with post-traumatic stress disorder.

  15. Altered White Matter Microstructure in Children with Attention-Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Nagel, Bonnie J.; Bathula, Deepti; Herting, Megan; Schmitt, Colleen; Kroenke, Christopher D.; Fair, Damien; Nigg, Joel T.

    2011-01-01

    Objective: Identification of biomarkers is a priority for attention-deficit/hyperactivity disorder (ADHD). Studies have documented macrostructural brain alterations in ADHD, but few have examined white matter microstructure, particularly in preadolescent children. Given dramatic white matter maturation across childhood, microstructural differences…

  16. 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

  17. Epigenetic modification of hippocampal Bdnf DNA in adult rats in an animal model of post-traumatic stress disorder.

    PubMed

    Roth, Tania L; Zoladz, Phillip R; Sweatt, J David; Diamond, David M

    2011-07-01

    Epigenetic alterations of the brain-derived neurotrophic factor (Bdnf) gene have been linked with memory, stress, and neuropsychiatric disorders. Here we examined whether there was a link between an established rat model of post-traumatic stress disorder (PTSD) and Bdnf DNA methylation. Adult male Sprague-Dawley rats were given psychosocial stress composed of two acute cat exposures in conjunction with 31 days of daily social instability. These manipulations have been shown previously to produce physiological and behavioral sequelae in rats that are comparable to symptoms observed in traumatized people with PTSD. We then assessed Bdnf DNA methylation patterns (at exon IV) and gene expression. We have found here that the psychosocial stress regimen significantly increased Bdnf DNA methylation in the dorsal hippocampus, with the most robust hypermethylation detected in the dorsal CA1 subregion. Conversely, the psychosocial stress regimen significantly decreased methylation in the ventral hippocampus (CA3). No changes in Bdnf DNA methylation were detected in the medial prefrontal cortex or basolateral amygdala. In addition, there were decreased levels of Bdnf mRNA in both the dorsal and ventral CA1. These results provide evidence that traumatic stress occurring in adulthood can induce CNS gene methylation, and specifically, support the hypothesis that epigenetic marking of the Bdnf gene may underlie hippocampal dysfunction in response to traumatic stress. Furthermore, this work provides support for the speculative notion that altered hippocampal Bdnf DNA methylation is a cellular mechanism underlying the persistent cognitive deficits which are prominent features of the pathophysiology of PTSD.

  18. Diagnosis and Management of Sleep Disorders in Posttraumatic Stress Disorder:A Review of the Literature

    PubMed Central

    Mohsenin, Shahla

    2014-01-01

    Objective: International and societal conflicts and natural disasters can leave physical and mental scars in people who are directly affected by these traumatic experiences. Posttraumatic stress disorder (PTSD) is the clinical manifestation of these experiences in the form of re-experiencing the trauma, avoidance of trauma-related stimuli, and persistent symptoms of hyperarousal. There is growing evidence that sleep disruption that occurs following trauma exposure may in fact contribute to the pathophysiology of PTSD and poor clinical outcomes. The purpose of this review is to highlight the importance of recognition and management of sleep disorders in patients with PTSD. Data Sources: English-language, adult research studies published between 1985 and April 2014 were identified via the PubMed database. The search terms used were PTSD AND sleep disorders. Study Selection: The search identified 792 original and review articles. Of these, 53 articles that discussed or researched sleep disorders in PTSD were selected. Fourteen randomized controlled trials of therapy for PTSD are included in this review. Results: Impaired sleep is a common complaint mainly in the form of nightmares and insomnia among people with PTSD. Sleep apnea and periodic limb movement disorder are particularly prevalent in patients with PTSD and, yet, remain unrecognized. Although selective serotonin reuptake inhibitors are effective in improving PTSD global symptoms, they have a variable and modest effect on sleep disorder symptoms. Cognitive-behavioral treatment targeted to sleep and/or the use of the centrally acting selective α1 antagonist prazosin have been more successful in treating insomnia and nightmares in PTSD than other classes of medications. In view of the high occurrence of sleep apnea and periodic leg movement disorder, a thorough sleep evaluation and treatment are warranted. Conclusions: Patients with PTSD have a high prevalence of sleep disorders and should be queried for

  19. Minireview: Stress-related psychiatric disorders with low cortisol levels: a metabolic hypothesis.

    PubMed

    Yehuda, Rachel; Seckl, Jonathan

    2011-12-01

    Several stress-associated neuropsychiatric disorders, notably posttraumatic stress disorder and chronic pain and fatigue syndromes, paradoxically exhibit somewhat low plasma levels of the stress hormone cortisol. The effects appear greatest in those initially traumatized in early life, implying a degree of developmental programming, perhaps of both lower cortisol and vulnerability to psychopathology. In these conditions, lowered cortisol is not due to any adrenal or pituitary insufficiency. Instead, two processes appear involved. First, there is increased target cell sensitivity to glucocorticoid action, notably negative feedback upon the hypothalamic-pituitary-adrenal (stress) axis. Altered density of the glucocorticoid receptor is inferred, squaring with much preclinical data showing early life challenges can permanently program glucocorticoid receptors in a tissue-specific manner. These effects involve epigenetic mechanisms. Second, early life trauma/starvation induces long-lasting lowering of glucocorticoid catabolism, specifically by 5α-reductase type 1 (predominantly a liver enzyme) and 11β-hydroxysteroid dehydrogenase type 2 (in kidney), an effect also seen in model systems. These changes reflect a plausible early-life adaptation to increase the persistence of active cortisol in liver (to maximize fuel output) and kidney (to increase salt retention) without elevation of circulating levels, thus avoiding their deleterious effects on brain and muscle. Modestly lowered circulating cortisol and increased vulnerability to stress-associated disorders may be the outcome. This notion implies a vulnerable early-life phenotype may be discernable and indicates potential therapy by modest glucocorticoid replacement. Indeed, early clinical trials with cortisol have shown a modicum of promise.

  20. Clinical Guidelines for Stellate Ganglion Block to Treat Anxiety Associated With Posttraumatic Stress Disorder

    DTIC Science & Technology

    2015-07-01

    post - traumatic stress disorder : a case report. Ann Clin Psychiatry. 2008;20:227–228. 5. Mulvaney SW...stellate gan- glion block in the treatment of anxiety symptoms from com- bat-related post - traumatic stress disorder : a case series. Mil Med... disorder . Mil Med. 2012:177:125–127. 9. Lipov EG, Navaie M, Brown PR, et al. Stellate ganglion block improves refractory post - traumatic stress disorder

  1. Posttraumatic stress disorder's dysphoria dimension and relations with generalized anxiety disorder symptoms.

    PubMed

    Durham, Tory A; Elhai, Jon D; Fine, Thomas H; Tamburrino, Marijo; Cohen, Gregory; Shirley, Edwin; Chan, Philip K; Liberzon, Israel; Galea, Sandro; Calabrese, Joseph R

    2015-07-30

    The present study investigated symptom relations between two highly comorbid disorders--posttraumatic stress disorder (PTSD) and generalized anxiety disorder (GAD)--by exploring their underlying dimensions. Based on theory and prior empirical research it was expected that the dysphoria factor of PTSD would be more highly related to GAD. As part of a longitudinal project of mental health among Ohio National Guard Soldiers, 1266 subjects were administered the Posttraumatic Stress Disorder Checklist (PCL) and Generalized Anxiety Disorder-7 scale (GAD-7). Confirmatory factor analyses (CFAs) were conducted to examine two models of PTSD and to determine which PTSD factors were more related to the GAD factor. The results indicate that the GAD factor was significantly more highly correlated with PTSD's dysphoria factor than with all other PTSD factors, including PTSD's reexperiencing factor, avoidance factor, and hyperarousal factor. Results indicate GAD was not significantly more highly correlated with numbing than most other factors of PTSD. The results are consistent with prior research. Implications of the results are discussed in regards to PTSD in DSM-5, comorbidity and diagnostic specificity.

  2. Suicidal behavior in adolescents with post-traumatic stress disorder.

    PubMed

    Ganz, D; Sher, L

    2010-08-01

    Recently, the prevalence of post-traumatic stress disorder (PTSD) in adolescence is higher than the prevalence of PTSD in adult populations. PTSD and suicidality are often found in populations of adolescents presenting with other emotional disorders (particularly mood disorders), traumatic grief, childhood abuse, and/or a family or peer history of suicide. The reasons and developments of the association between PTSD and suicidality in adolescence, however, remain unclear. Core psychobiological changes contributing to PTSD affect emotion, arousal, perception of the self and the world, irritability, impulsivity, anger, aggression and depression. There is evidence that the aforementioned factors, as well as alcohol and other drug use may act to moderate the influence of stressful life events and lead to eventual suicidality. Both PTSD and suicidality in adolescents have also been hypothesized to be a result of exposure to violence and negative coping styles. There are many treatment challenges for these populations, yet the most promising prevention and treatments include suicide risk screenings, suicide education, Dialectical Behavioral Therapy, addressing associated coping mechanisms and prescribing anti-depressant and anti-anxiety medications. However, when prescribing medications, physicians do need to be careful to consider the weaknesses and strengths of each of the pharmacological options as they apply to adolescents presenting with PTSD and suicidality.

  3. Folding propensity of intrinsically disordered proteins by osmotic stress

    DOE PAGES

    Mansouri, Amanda L.; Grese, Laura N.; Rowe, Erica L.; ...

    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 scatteringmore » (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.« less

  4. Internalizing disorders and leukocyte telomere erosion: a prospective study of depression, generalized anxiety disorder and post-traumatic stress disorder.

    PubMed

    Shalev, I; Moffitt, T E; Braithwaite, A W; Danese, A; Fleming, N I; Goldman-Mellor, S; Harrington, H L; Houts, R M; Israel, S; Poulton, R; Robertson, S P; Sugden, K; Williams, B; Caspi, A

    2014-11-01

    There is evidence that persistent psychiatric disorders lead to age-related disease and premature mortality. Telomere length has emerged as a promising biomarker in studies that test the hypothesis that internalizing psychiatric disorders are associated with accumulating cellular damage. We tested the association between the persistence of internalizing disorders (depression, generalized anxiety disorder and post-traumatic stress disorder) and leukocyte telomere length (LTL) in the prospective longitudinal Dunedin Study (n=1037). Analyses showed that the persistence of internalizing disorders across repeated assessments from ages 11 to 38 years predicted shorter LTL at age 38 years in a dose-response manner, specifically in men (β=-0.137, 95% confidence interval (CI): -0.232, -0.042, P=0.005). This association was not accounted for by alternative explanatory factors, including childhood maltreatment, tobacco smoking, substance dependence, psychiatric medication use, poor physical health or low socioeconomic status. Additional analyses using DNA from blood collected at two time points (ages 26 and 38 years) showed that LTL erosion was accelerated among men who were diagnosed with internalizing disorder in the interim (β=-0.111, 95% CI: -0.184, -0.037, P=0.003). No significant associations were found among women in any analysis, highlighting potential sex differences in internalizing-related telomere biology. These findings point to a potential mechanism linking internalizing disorders to accelerated biological aging in the first half of the life course, particularly in men. Because internalizing disorders are treatable, the findings suggest the hypothesis that treating psychiatric disorders in the first half of the life course may reduce the population burden of age-related disease and extend health expectancy.

  5. Salt stress alters DNA methylation levels in alfalfa (Medicago spp).

    PubMed

    Al-Lawati, A; Al-Bahry, S; Victor, R; Al-Lawati, A H; Yaish, M W

    2016-02-26

    Modification of DNA methylation status is one of the mechanisms used by plants to adjust gene expression at both the transcriptional and posttranscriptional levels when plants are exposed to suboptimal conditions. Under abiotic stress, different cultivars often show heritable phenotypic variation accompanied by epigenetic polymorphisms at the DNA methylation level. This variation may provide the raw materials for plant breeding programs that aim to enhance abiotic stress tolerance, including salt tolerance. In this study, methylation-sensitive amplified polymorphism (MSAP) analysis was used to assess cytosine methylation levels in alfalfa (Medicago spp) roots exposed to increasing NaCl concentrations (0.0, 8.0, 12.0, and 20.0 dS/m). Eleven indigenous landraces were analyzed, in addition to a salt-tolerant cultivar that was used as a control. There was a slight increase in DNA methylation upon exposure to high levels of soil salinity. Phylogenetic analysis using MSAP showed epigenetic variation within and between the alfalfa landraces when exposed to saline conditions. Based on MSAP and enzyme-linked immunosorbent assay results, we found that salinity increased global DNA methylation status, particularly in plants exposed to the highest level of salinity (20 dS/m). Quantitative reverse transcription-polymerase chain reaction indicated that this might be mediated by the overexpression of methyltransferase homolog genes after exposure to saline conditions. DNA demethylation using 5-azacytidine reduced seedling lengths and dry and fresh weights, indicating a possible decrease in salinity tolerance. These results suggest that salinity affects DNA methylation flexibility.

  6. Subregional Shape Alterations in the Amygdala in Patients with Panic Disorder

    PubMed Central

    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

    Background 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. Methods 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. Results 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). Conclusions 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. PMID:27336300

  7. Treatment Outcome-Related White Matter Differences in Veterans with Posttraumatic Stress Disorder

    PubMed Central

    Kennis, Mitzy; van Rooij, Sanne J H; Tromp, Do P M; Fox, Andrew S; Rademaker, Arthur R; Kahn, René S; Kalin, Ned H; Geuze, Elbert

    2015-01-01

    Posttraumatic stress disorder (PTSD) is a debilitating disorder that has been associated with brain abnormalities, including white matter alterations. However, little is known about the effect of treatment on these brain alterations. To investigate the course of white matter alterations in PTSD, we used a longitudinal design investigating treatment effects on white matter integrity using diffusion tensor imaging (DTI). Diffusion tensor and magnetization transfer images were obtained pre- and posttreatment from veterans with (n=39) and without PTSD (n=22). After treatment, 16 PTSD patients were remitted, and 23 had persistent PTSD based on PTSD diagnosis. The dorsal and hippocampal cingulum bundle, stria terminalis, and fornix were investigated as regions of interest. Exploratory whole-brain analyses were also performed. Groups were compared with repeated-measures ANOVA for fractional anisotropy (FA), and magnetization transfer ratio. Persistently symptomatic PTSD patients had increasing FA of the dorsal cingulum over time, and at reassessment these FA values were higher than both combat controls and the remitted PTSD group. Group-by-time interactions for FA were found in the hippocampal cingulum, fornix, and stria terminalis, posterior corona radiata, and superior longitudinal fasciculus. Our results indicate that higher FA of the dorsal cingulum bundle may be an acquired feature of persistent PTSD that develops over time. Furthermore, treatment might have differential effects on the hippocampal cingulum, fornix, stria terminalis, posterior corona radiata, and superior longitudinal fasciculus in remitted vs persistent PTSD patients. This study contributes to a better understanding of the neural underpinnings of PTSD treatment outcome. PMID:25837284

  8. Blood gene expression profiles suggest altered immune function associated with symptoms of generalized anxiety disorder

    PubMed Central

    Wingo, Aliza P.; Gibson, Greg

    2014-01-01

    Prospective epidemiological studies found that generalized anxiety disorder (GAD) can impair immune function and increase risk for cardiovascular disease or events. Mechanisms underlying the physiological reverberations of anxiety, however, are still elusive. Hence, we aimed to investigate molecular processes mediating effects of anxiety on physical health using blood gene expression profiles of 336 community participants (157 anxious and 179 control). We examined genome-wide differential gene expression in anxiety, as well as associations between nine major modules of co-regulated transcripts in blood gene expression and anxiety. No significant differential expression was observed in women, but 631 genes were differentially expressed between anxious and control men at the false discovery rate of 0.1 after controlling for age, body mass index, race, and batch effect. Gene set enrichment analysis (GSEA) revealed that genes with altered expression levels in anxious men were involved in response of various immune cells to vaccination and to acute viral and bacterial infection, and in a metabolic network affecting traits of metabolic syndrome. Further, we found one set of 260 co-regulated genes to be significantly associated with anxiety in men after controlling for the relevant covariates, and demonstrate its equivalence to a component of the stress-related conserved transcriptional response to adversity profile. Taken together, our results suggest potential molecular pathways that can explain negative effects of GAD observed in epidemiological studies. Remarkably, even mild anxiety, which most of our participants had, was associated with observable changes in immune-related gene expression levels. Our findings generate hypotheses and provide incremental insights into molecular mechanisms mediating negative physiological effects of GAD. PMID:25300922

  9. Blood gene expression profiles suggest altered immune function associated with symptoms of generalized anxiety disorder.

    PubMed

    Wingo, Aliza P; Gibson, Greg

    2015-01-01

    Prospective epidemiological studies found that generalized anxiety disorder (GAD) can impair immune function and increase risk for cardiovascular disease or events. Mechanisms underlying the physiological reverberations of anxiety, however, are still elusive. Hence, we aimed to investigate molecular processes mediating effects of anxiety on physical health using blood gene expression profiles of 336 community participants (157 anxious and 179 control). We examined genome-wide differential gene expression in anxiety, as well as associations between nine major modules of co-regulated transcripts in blood gene expression and anxiety. No significant differential expression was observed in women, but 631 genes were differentially expressed between anxious and control men at the false discovery rate of 0.1 after controlling for age, body mass index, race, and batch effect. Gene set enrichment analysis (GSEA) revealed that genes with altered expression levels in anxious men were involved in response of various immune cells to vaccination and to acute viral and bacterial infection, and in a metabolic network affecting traits of metabolic syndrome. Further, we found one set of 260 co-regulated genes to be significantly associated with anxiety in men after controlling for the relevant covariates, and demonstrate its equivalence to a component of the stress-related conserved transcriptional response to adversity profile. Taken together, our results suggest potential molecular pathways that can explain negative effects of GAD observed in epidemiological studies. Remarkably, even mild anxiety, which most of our participants had, was associated with observable changes in immune-related gene expression levels. Our findings generate hypotheses and provide incremental insights into molecular mechanisms mediating negative physiological effects of GAD.

  10. Sleep Alterations Following Exposure to Stress Predict Fear-Associated Memory Impairments in a Rodent Model of PTSD

    PubMed Central

    Vanderheyden, William M.; George, Sophie A.; Urpa, Lea; Kehoe, Michaela; Liberzon, Israel; Poe, Gina R.

    2015-01-01

    Sleep abnormalities such as insomnia, nightmares, hyper-arousal, and difficulty initiating or maintaining sleep, are diagnostic criteria of post-traumatic stress disorder (PTSD). The vivid dream state, rapid eye movement (REM) sleep, has been implicated in processing emotional memories. We have hypothesized that REM sleep is maladaptive in those suffering from PTSD. However, the precise neurobiological mechanisms regulating these sleep disturbances following trauma exposure are poorly understood. Using single prolonged stress (SPS), a well-validated rodent model of PTSD, we measured sleep alterations in response to stress exposure and over a subsequent 7-day isolation period during which the PTSD-like phenotype develops in rats. SPS resulted in acutely increased REM sleep, transition to REM sleep, and decreased waking in addition to alterations in sleep architecture. The severity of the PTSD-like phenotype was later assessed by measuring freezing levels on a fear-associated memory test. Interestingly, the change in REM sleep following SPS was significantly correlated with freezing behavior during extinction recall assessed more than a week later. We also report reductions in theta (4–10 Hz) and sigma (10–15 Hz) band power during transition to REM sleep which also correlated with impaired fear-associated memory processing. These data reveal that changes in REM sleep, transition to REM sleep, waking, and theta and sigma power may serve as sleep biomarkers to identify individuals with increased susceptibility to PTSD following trauma exposure. PMID:26019008

  11. Possible Risk Factors for Acute Stress Disorder and Post-Traumatic Stress Disorder After an Industrial Explosion

    PubMed Central

    TAYMUR, İbrahim; SARGIN, A. Emre; ÖZDEL, Kadir; TÜRKÇAPAR, Hakan M.; ÇALIŞGAN, Lale; ZAMKI, Erkut; DEMİREL, Başak

    2014-01-01

    Introduction There have been deaths and injuries after an explosion which happened in an industrial region in Ankara in February 2011. The aim of this study was to determine the prevalence of acute stress disorder (ASD) and posttraumatic stress disorder (PTSD), and to determine the variables which can be the risk factors for PTSD. Methods In this study, we included a total of 197 subjects who were present at the factory building and at the four offices nearby when the disaster occurred. All the participants were assessed one month after the explosion and 157 of them were reassessed six months after the explosion. Socio-demographic information forms were given and the Clinician-Administered PTSD Scale (CAPS) was administered to the participants one month after the explosion. Psychiatric assessments were done using the structured clinical interview for DSM-IV axis-I disorders (SCID-I). The CAPS was re-applied six month after the disaster. Results At the first-month assessments, ASD was detected in 37.1% of participants and PTSD in 13.7%, whereas PTSD was observed in 16.6% of subjects at the sixth month of the accident. According to the first month data, having any psychiatric disorder before the incident, physical injury, acquaintances among the dead and the injured people, being involved in the incident and seeing dead people were detected as the risk factors for PTSD. At the sixth month assessment, physical injury, acquaintances among the dead and the injured, being involved in the incident were seen as risk factors for PTSD. Conclusion ASD and PTSD can be seen after an explosion. Having a previous psychiatric disorder and being directly affected by trauma and being injured are the risk factors for PTSD. This study implies that preventive mental health care services should include the management of current psychiatric condition and employee safety issues.

  12. Tailoring therapeutic strategies for treating posttraumatic stress disorder symptom clusters

    PubMed Central

    Norrholm, Seth D; Jovanovic, Tanja

    2010-01-01

    According to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, posttraumatic stress disorder (PTSD) is characterized by three major symptom clusters following an event that elicited fear, helplessness, or horror. This review will examine each symptom cluster of PTSD separately, giving case study examples of patients who exhibit a preponderance of a given symptom domain. We use a translational approach in describing the underlying neurobiology that is relevant to particular symptoms and treatment options, thus showing how clinical practice can benefit from current research. By focusing on symptom clusters, we provide a more specific view of individual patient’s clinical presentations, in order to better address treatment needs. Finally, the review will also address potential genetic approaches to treatment as another form of individualized treatment. PMID:20856915

  13. Reduced Specificity in Episodic Future Thinking in Posttraumatic Stress Disorder

    PubMed Central

    Graham, Belinda; Fihosy, Sonia; Stott, Richard; Ehlers, Anke

    2014-01-01

    Posttraumatic stress disorder (PTSD), one of the most common disorders following trauma, has been associated with a tendency to remember past personal memories in a nonspecific, overgeneral way. The present study investigated whether such a bias also applies to projections of future personal events. Trauma survivors (N = 50) generated brief descriptions of imagined future experiences in response to positive and negative cues in a future-based Autobiographical Memory Test. Survivors with PTSD imagined fewer specific future events in response to positive, but not to negative, cues, compared to those without PTSD. This effect was independent of comorbid major depression. Reduced memory specificity in response to positive cues was related to appraisals of foreshortened future and permanent change. Training to enhance specificity of future projections may be helpful in PTSD and protect against potentially toxic effects of autobiographical memory overgenerality. PMID:24926418

  14. Factors related to posttraumatic stress disorder in adolescence.

    PubMed

    Nooner, Kate B; Linares, L Oriana; Batinjane, Jessica; Kramer, Rachel A; Silva, Raul; Cloitre, Marylene

    2012-07-01

    Studies of posttraumatic stress disorder (PTSD) in adolescence published from 2000 to 2011 indicate that adolescents are at greater risk of experiencing trauma than either adults or children, and that the prevalence of PTSD among adolescents is 3-57%. Age, gender, type of trauma, and repeated trauma are discussed as factors related to the increased rates of adolescent PTSD. PTSD in adolescence is also associated with suicide, substance abuse, poor social support, academic problems, and poor physical health. PTSD may disrupt biological maturational processes and contribute to the long-term emotion and behavior regulation problems that are often evident in adolescents with the disorder. Recommendations are presented for practice and research regarding the promotion of targeted prevention and intervention services to maximize adolescents' strengths and minimize vulnerabilities. Public policy implications are discussed.

  15. Post-traumatic stress disorder in children and adolescents.

    PubMed

    Chowdhury, Uttom; Pancha, Amit

    2011-12-01

    Post-traumatic stress disorder (PTSD) is a syndrome defined by the intrusive re-experiencing of trauma, avoidance of reminders of the trauma and increased hyperarousal. Although the condition is well established in adults, there is little research into PTSD in children and adolescents. The available research shows that young people experience similar symptoms to adults. Risk factors include family dysfunction, peer problems, greater exposure to the trauma and the presence of pre-existing psychiatric disorder such as anxiety. Protective factors include good coping skills, good relationship with a parent and support from others in the community. This article reviews treatment approaches to PTSD in young people in particular the use of cognitive behavioural therapy (CBT).

  16. Mitochondrial dysfunction, oxidative stress, and major depressive disorder

    PubMed Central

    Tobe, Edward H

    2013-01-01

    There is controversy about depression being a physical illness, in part because a reproducible, sensitive, and specific biologic marker is not available. However, there is evidence that mitochondrial dysfunction and oxidative stress may be associated with abnormal brain function and mood disorders, such as depression. This paper reviews selected human and animal studies providing evidence that intracellular mitochondrial metabolic dysfunction in specific brain regions is associated with major depressive disorder. This supports the hypothesis that chronic mitochondrial dysfunction in specific tissues may be associated with depression. Evaluation of mitochondrial dysfunction in specific tissues may broaden the perspective of depression beyond theories about neurotransmitters or receptor sites, and may explain the persistent signs and symptoms of depression. PMID:23650447

  17. Epidemiology of trauma and posttraumatic stress disorder in Mexico.

    PubMed

    Norris, Fran H; Murphy, Arthur D; Baker, Charlene K; Perilla, Julia L; Rodriguez, Francisco Gutiérrez; Rodriguez, José de Jesús Gutiérrez

    2003-11-01

    Prevalence rates of trauma and posttraumatic stress disorder (PTSD) were estimated from a probability sample of 2,509 adults from 4 cities in Mexico. PTSD was assessed according to Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 1994) criteria using the Composite International Diagnostic Interview (CIDI; WHO, 1997). Lifetime prevalence of exposure and PTSD were 76% and 11.2%, respectively. Risk for PTSD was highest in Oaxaca (the poorest city), persons of lower socioeconomic status, and women. Conditional risk for PTSD was highest following sexual violence, but nonsexual violence and traumatic bereavement had greater overall impact because of their frequency. Of lifetime cases, 62% became chronic; only 42% received medical or professional care. The research demonstrates the importance of expanding the epidemiologic research base on trauma to include developing countries around the world.

  18. Contrasting exposure and experiential therapies for complex posttraumatic stress disorder.

    PubMed

    Gleiser, Kari; Ford, Julian D; Fosha, Diana

    2008-09-01

    In this paper, the authors compare and contrast two psychotherapy paradigms for the treatment of complex posttraumatic stress disorder (PTSD): a behavioral therapy (prolonged exposure; PE) and an experiential therapy (Accelerated Experiential Dynamic Psychotherapy; AEDP). PE has received strong research support as an effective treatment for PTSD. The scientific evidence for experiential therapy is sparser, but also positive. In addition, clinical and research evidence suggest that (a) experiential processes are inherently embedded in PE, and may influence PE outcomes; and that (b) AEDP addresses several clinical and relational factors that are negative prognostic factors for PE (e.g., affect dysregulation, disorganized attachment, sense of alienation and mental defeat, dissociation, and disorders of the self). Suggestions are provided for further empirical exploration of the process and efficacy of AEDP and experientially informed PE for complex cases of PTSD. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

  19. Biological studies of post-traumatic stress disorder.

    PubMed

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

    2012-11-01

    Post-traumatic stress disorder (PTSD) is the only major mental disorder for which a cause is considered to be known: that is, 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. This Review attempts to present the current state of this understanding on the basis of psychophysiological, structural and functional neuroimaging, and endocrinological, genetic and molecular biological studies in humans and in animal models.

  20. Peritraumatic reactions and posttraumatic stress disorder in psychiatrically impaired youth.

    PubMed

    Sugar, Jeff; Ford, Julian D

    2012-02-01

    Although peritraumatic dissociation and other subjective peritraumatic reactions, such as emotional distress and arousal, have been shown to affect the relationship between a traumatic event and the development of posttraumatic stress disorder (PTSD) in adults, systematic studies with youth have not been done. In a mixed ethnic and racial sample of 90 psychiatrically impaired youth (ages 10-18, 56% boys), we investigated the contributions of peritraumatic dissociation, emotional distress, and arousal to current PTSD severity after accounting for the effects of gender, trauma history, trait dissociation, and psychopathology (attention-deficit/hyperactivity disorder and depression). Peritraumatic dissociation emerged as the only peritraumatic variable associated with current PTSD severity assessed both by questionnaire and interview methods (β = .30 and .47 p < .01). Peritraumatic dissociation can be rapidly assessed in clinical practice and warrants further testing in prospective studies as a potential mediator of the trauma-PTSD relationship in youth.

  1. Stress habituation and alterations in perceived stress predict BMI percentile changes across a school year

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adolescents experience stressful situations at a high rate during school. Indeed, school is the most common source of stress for teens. This high rate of stress may promote increases in adiposity during a developmental period important for establishing the adult physique. Adiposity gains may be th...

  2. Stroop-interference effect in post-traumatic stress disorder.

    PubMed

    Cui, Hong; Chen, Guoliang; Liu, Xiaohui; Shan, Moshui; Jia, Yanyan

    2014-12-01

    To investigate the conflict processing in posttraumatic stress disorder (PTSD) patients, we conducted the classical Stroop task by recording event-related potentials. Although the reaction time was overall slower for PTSD patients than healthy age-matched control group, the Stroop-interference effect of reaction time did not differ between the two groups. Compared with normal controls, the interference effects of N 2 and N 450 components were larger and the interference effect of slow potential component disappeared in PTSD. These data indicated the dysfunction of conflict processing in individuals with PTSD.

  3. The validity of posttraumatic stress disorder among Vietnamese refugees.

    PubMed

    Fawzi, M C; Pham, T; Lin, L; Nguyen, T V; Ngo, D; Murphy, E; Mollica, R F

    1997-01-01

    The aim of this study was to examine the validity of posttraumatic stress disorder (PTSD) among Vietnamese refugees. The study population included 74 Vietnamese refugees who had resettled in the metropolitan Boston area. The previously validated Harvard Trauma Questionnaire was used to assess traumatic events and trauma-related symptoms. The number of traumatic events experienced was positively correlated with the severity of PTSD-related symptoms in this population. Internal consistency estimates and principal components analysis provided results that generally supported DSM-IV symptom dimensions of arousal, avoidance, and reexperiencing. However, the emergence of two separate dimensions of avoidance reflected the important contribution of depression to the traumatic response.

  4. Animal models of post-traumatic stress disorder: face validity

    PubMed Central

    Goswami, Sonal; Rodríguez-Sierra, Olga; Cascardi, Michele; Paré, Denis

    2013-01-01

    Post-traumatic stress disorder (PTSD) is a debilitating condition that develops in a proportion of individuals following a traumatic event. Despite recent advances, ethical limitations associated with human research impede progress in understanding PTSD. Fortunately, much effort has focused on developing animal models to help study the pathophysiology of PTSD. Here, we provide an overview of animal PTSD models where a variety of stressors (physical, psychosocial, or psychogenic) are used to examine the long-term effects of severe trauma. We emphasize models involving predator threat because they reproduce human individual differences in susceptibility to, and in the long-term consequences of, psychological trauma. PMID:23754973

  5. Posttraumatic stress disorder, depression, and suicide in veterans.

    PubMed

    Sher, Leo; Braquehais, María Dolores; Casas, Miquel

    2012-02-01

    Suicidal behavior is a critical problem in war veterans. Combat veterans are not only more likely to have suicidal ideation, often associated with posttraumatic stress disorder (PTSD) and depression, but they are more likely to act on a suicidal plan. Especially since veterans may be less likely to seek help from a mental health professional, non-mental-health physicians are in a key position to screen for PTSD, depression, and suicidal ideation in these patients. The authors discuss the association of PTSD, depression, and suicide in veterans, keys to assessment of suicide risk, and interventions.

  6. Posttraumatic stress disorder and dementia in Holocaust survivors.

    PubMed

    Sperling, Wolfgang; Kreil, Sebastian Konstantin; Biermann, Teresa

    2011-03-01

    The incidence of mental and somatic sequelae has been shown to be very high in the group of people damaged by the Holocaust. Within the context of internal research, 93 Holocaust survivors suffering from posttraumatic stress disorder have been examined. Patients suffered on average from 4.5 (standard deviation ± 1.8) somatic diagnoses as well as 1.8 (standard deviation ± 0.5) psychiatric diagnoses. A diagnosis of dementia was ascertained according to ICD-10 criteria in 14%. Vascular dementia (66%) dominated over Alzheimer's dementia (23%) and other subtypes (11%).

  7. From Soldiers to Children: Developmental Sciences Transform the Construct of Posttraumatic Stress Disorder

    ERIC Educational Resources Information Center

    Franks, Bridget A.

    2014-01-01

    Posttraumatic stress disorder (PTSD) was first included in the American Psychiatric Association's "Diagnostic and statistical manual of mental disorders" in 1980. Long used to describe the reactions of soldiers affected by stress in combat situations, PTSD is now recognised as a disorder affecting abused and neglected infants and…

  8. Altered Lipid Homeostasis in Sertoli Cells Stressed by Mild Hyperthermia

    PubMed Central

    Vallés, Ana S.; Aveldaño, Marta I.; Furland, Natalia E.

    2014-01-01

    Spermatogenesis is known to be vulnerable to temperature. Exposures of rat testis to moderate hyperthermia result in loss of germ cells with survival of Sertoli cells (SC). Because SC provide structural and metabolic support to germ cells, our aim was to test the hypothesis that these exposures affect SC functions, thus contributing to germ cell damage. In vivo, regularly repeated exposures (one of 15 min per day, once a day during 5 days) of rat testes to 43°C led to accumulation of neutral lipids. This SC-specific lipid function took 1–2 weeks after the last of these exposures to be maximal. In cultured SC, similar daily exposures for 15 min to 43°C resulted in significant increase in triacylglycerol levels and accumulation of lipid droplets. After incubations with [3H]arachidonate, the labeling of cardiolipin decreased more than that of other lipid classes. Another specifically mitochondrial lipid metabolic function, fatty acid oxidation, also declined. These lipid changes suggested that temperature affects SC mitochondrial physiology, which was confirmed by significantly increased degrees of membrane depolarization and ROS production. This concurred with reduced expression of two SC-specific proteins, transferrin, and Wilms' Tumor 1 protein, markers of SC secretion and differentiation functions, respectively, and with an intense SC cytoskeletal perturbation, evident by loss of microtubule network (α-tubulin) and microfilament (f-actin) organization. Albeit temporary and potentially reversible, hyperthermia-induced SC structural and metabolic alterations may be long-lasting and/or extensive enough to respond for the decreased survival of the germ cells they normally foster. PMID:24690895

  9. Posttraumatic Stress Disorder and Co-Occurring Substance Use Disorders: Advances in Assessment and Treatment

    PubMed Central

    McCauley, Jenna L; Killeen, Therese; Gros, Daniel F.; Brady, Kathleen T.; Back, Sudie E.

    2013-01-01

    Posttraumatic stress disorder (PTSD) and substance use disorders (SUDs) are prevalent and frequently co-occur. Comorbid PTSD/SUD is associated with a more complex and costly clinical course when compared with either disorder alone, including increased chronic physical health problems, poorer social functioning, higher rates of suicide attempts, more legal problems, increased risk of violence, worse treatment adherence, and less improvement during treatment. In response, psychosocial treatment options have increased substantially over the past decade and integrated approaches – treatments that address symptoms of both PTSD and SUD concurrently –are fast becoming the preferred model for treatment. This paper reviews the prevalence, etiology and assessment practices as well as advances in the behavioral and pharmacologic treatment of comorbid PTSD and SUDs. PMID:24179316

  10. Mind-body Practices for Posttraumatic Stress Disorder

    PubMed Central

    Kim, Sang Hwan; Schneider, Suzanne M.; Kravitz, Len; Mermier, Christine; Burge, Mark R.

    2013-01-01

    Background Mind-body practices are increasingly used to provide stress reduction for posttraumatic stress disorder (PTSD). Mind-body practice encompasses activities with the intent to use the mind to impact physical functioning and improve health. Methods This is a literature review using PubMed, PsycINFO, and PILOTS to identify the effects of mind-body intervention modalities, such as yoga, taichi, qigong, mindfulness-based stress reduction, meditation, and deep breathing, as interventions for PTSD. Results The literature search identified 92 articles, only 16 of which were suitable for inclusion in this review. We reviewed only original, full text articles that met the inclusion criteria. Most of the studies have small sample size, but findings from the 16 publications reviewed here suggest that mind-body practices are associated with positive impacts on PTSD symptoms. Mind-body practices incorporate numerous therapeutic effects on stress responses, including reductions in anxiety, depression, and anger, and increases in pain-tolerance, self-esteem, energy levels, ability to relax, and ability to cope with stressful situations. In general, mind-body practices were found to be a viable intervention to improve the constellation of PTSD symptoms such as intrusive memories, avoidance, and increased emotional arousal. Conclusions Mind-body practices are increasingly employed in the treatment of PTSD and are associated with positive impacts on stress-induced illnesses such as depression and PTSD in most existing studies. Knowledge about the diverse modalities of mind-body practices may provide clinicians and patients with the opportunity to explore an individualized and effective treatment plan enhanced by mind-body interventions as part of ongoing self-care. PMID:23609463

  11. White Matter Abnormalities in Post-traumatic Stress Disorder Following a Specific Traumatic Event.

    PubMed

    Li, Lei; Lei, Du; Li, Lingjiang; Huang, Xiaoqi; Suo, Xueling; Xiao, Fenglai; Kuang, Weihong; Li, Jin; Bi, Feng; Lui, Su; Kemp, Graham J; Sweeney, John A; Gong, Qiyong

    2016-02-01

    Studies of posttraumatic stress disorder (PTSD) are complicated by wide variability in the intensity and duration of prior stressors in patient participants, secondary effects of chronic psychiatric illness, and a variable history of treatment with psychiatric medications. In magnetic resonance imaging (MRI) studies, patient samples have often been small, and they were not often compared to similarly stressed patients without PTSD in order to control for general stress effects. Findings from these studies have been inconsistent. The present study investigated whole-brain microstructural alterations of white matter in a large drug-naive population who survived a specific, severe traumatic event (a major 8.0-magnitude earthquake). Using diffusion tensor imaging (DTI), we explored group differences between 88 PTSD patients and 91 matched traumatized non-PTSD controls in fractional anisotropy (FA), as well as its component elements axial diffusivity (AD) and radial diffusivity (RD), and examined these findings in relation to findings from deterministic DTI tractography. Relations between white matter alterations and psychiatric symptom severity were examined. PTSD patients, relative to similarly stressed controls, showed an FA increase as well as AD and RD changes in the white matter beneath left dorsolateral prefrontal cortex and forceps major. The observation of increased FA in the PTSD group suggests that the pathophysiology of PTSD after a specific acute traumatic event is distinct from what has been reported in patients with several years duration of illness. Alterations in dorsolateral prefrontal cortex may be an important aspect of illness pathophysiology, possibly via the region's established role in fear extinction circuitry. Use-dependent myelination or other secondary compensatory changes in response to heightened demands for threat appraisal and emotion regulation may be involved.

  12. White Matter Abnormalities in Post-traumatic Stress Disorder Following a Specific Traumatic Event

    PubMed Central

    Li, Lei; Lei, Du; Li, Lingjiang; Huang, Xiaoqi; Suo, Xueling; Xiao, Fenglai; Kuang, Weihong; Li, Jin; Bi, Feng; Lui, Su; Kemp, Graham J.; Sweeney, John A.; Gong, Qiyong

    2016-01-01

    Studies of posttraumatic stress disorder (PTSD) are complicated by wide variability in the intensity and duration of prior stressors in patient participants, secondary effects of chronic psychiatric illness, and a variable history of treatment with psychiatric medications. In magnetic resonance imaging (MRI) studies, patient samples have often been small, and they were not often compared to similarly stressed patients without PTSD in order to control for general stress effects. Findings from these studies have been inconsistent. The present study investigated whole-brain microstructural alterations of white matter in a large drug-naive population who survived a specific, severe traumatic event (a major 8.0-magnitude earthquake). Using diffusion tensor imaging (DTI), we explored group differences between 88 PTSD patients and 91 matched traumatized non-PTSD controls in fractional anisotropy (FA), as well as its component elements axial diffusivity (AD) and radial diffusivity (RD), and examined these findings in relation to findings from deterministic DTI tractography. Relations between white matter alterations and psychiatric symptom severity were examined. PTSD patients, relative to similarly stressed controls, showed an FA increase as well as AD and RD changes in the white matter beneath left dorsolateral prefrontal cortex and forceps major. The observation of increased FA in the PTSD group suggests that the pathophysiology of PTSD after a specific acute traumatic event is distinct from what has been reported in patients with several years duration of illness. Alterations in dorsolateral prefrontal cortex may be an important aspect of illness pathophysiology, possibly via the region's established role in fear extinction circuitry. Use-dependent myelination or other secondary compensatory changes in response to heightened demands for threat appraisal and emotion regulation may be involved. PMID:26981581

  13. Executive Dysfunctions: The Role in Attention Deficit Hyperactivity and Post-traumatic Stress Neuropsychiatric Disorders

    PubMed Central

    Martínez, Lía; Prada, Edward; Satler, Corina; Tavares, Maria C. H.; Tomaz, Carlos

    2016-01-01

    Executive functions (EFs) is an umbrella term for various cognitive processes controlled by a complex neural activity, which allow the production of different types of behaviors seeking to achieve specific objectives, one of them being inhibitory control. There is a wide consensus that clinical and behavioral alterations associated with EF, such as inhibitory control, are present in various neuropsychiatric disorders. This paper reviews the research literature on the relationship between executive dysfunction, frontal-subcortical neural circuit changes, and the psychopathological processes associated with attention deficit hyperactivity disorder (ADHD) and post-traumatic stress disorder (PTSD). A revision on the role of frontal-subcortical neural circuits and their presumable abnormal functioning and the high frequency of neuropsychiatric symptoms could explain the difficulties with putting effector mechanisms into action, giving individuals the necessary tools to act efficiently in their environment. Although, neuronal substrate data about ADHD and PTSD has been reported in the literature, it is isolated. Therefore, this review highlights the overlapping of neural substrates in the symptomatology of ADHD and PTSD disorders concerning EFs, especially in the inhibitory component. Thus, the changes related to impaired EF that accompany disorders like ADHD and PTSD could be explained by disturbances that have a direct or indirect impact on the functioning of these loops. Initially, the theoretical model of EF according to current neuropsychology will be presented, focusing on the inhibitory component. In a second stage, this component will be analyzed for each of the disorders of interest, considering the clinical aspects, the etiology and the neurobiological basis. Additionally, commonalities between the two neuropsychiatric conditions will be taken into consideration from the perspectives of cognitive and emotional inhibition. Finally, the implications and future

  14. 38 CFR 4.129 - Mental disorders due to traumatic stress.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Mental disorders due to traumatic stress. 4.129 Section 4.129 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... traumatic stress. When a mental disorder that develops in service as a result of a highly stressful event...

  15. 38 CFR 4.129 - Mental disorders due to traumatic stress.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Mental disorders due to traumatic stress. 4.129 Section 4.129 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... traumatic stress. When a mental disorder that develops in service as a result of a highly stressful event...

  16. 38 CFR 4.129 - Mental disorders due to traumatic stress.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Mental disorders due to traumatic stress. 4.129 Section 4.129 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... traumatic stress. When a mental disorder that develops in service as a result of a highly stressful event...

  17. 38 CFR 4.129 - Mental disorders due to traumatic stress.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Mental disorders due to traumatic stress. 4.129 Section 4.129 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... traumatic stress. When a mental disorder that develops in service as a result of a highly stressful event...

  18. 38 CFR 4.129 - Mental disorders due to traumatic stress.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Mental disorders due to traumatic stress. 4.129 Section 4.129 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... traumatic stress. When a mental disorder that develops in service as a result of a highly stressful event...

  19. Maternal chewing during prenatal stress ameliorates stress-induced hypomyelination, synaptic alterations, and learning impairment in mouse offspring.

    PubMed

    Suzuki, Ayumi; Iinuma, Mitsuo; Hayashi, Sakurako; Sato, Yuichi; Azuma, Kagaku; Kubo, Kin-Ya

    2016-11-15

    Maternal chewing during prenatal stress attenuates both the development of stress-induced learning deficits and decreased cell proliferation in mouse hippocampal dentate gyrus. Hippocampal myelination affects spatial memory and the synaptic structure is a key mediator of neuronal communication. We investigated whether maternal chewing during prenatal stress ameliorates stress-induced alterations of hippocampal myelin and synapses, and impaired development of spatial memory in adult offspring. Pregnant mice were divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube, and was initiated on day 12 of pregnancy and continued until delivery. Mice in the stress/chewing group were given a wooden stick to chew during restraint. In 1-month-old pups, spatial memory was assessed in the Morris water maze, and hippocampal oligodendrocytes and synapses in CA1 were assayed by immunohistochemistry and electron microscopy. Prenatal stress led to impaired learning ability, and decreased immunoreactivity of myelin basic protein (MBP) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in the hippocampal CA1 in adult offspring. Numerous myelin sheath abnormalities were observed. The G-ratio [axonal diameter to axonal fiber diameter (axon plus myelin sheath)] was increased and postsynaptic density length was decreased in the hippocampal CA1 region. Maternal chewing during stress attenuated the prenatal stress-induced impairment of spatial memory, and the decreased MBP and CNPase immunoreactivity, increased G-ratios, and decreased postsynaptic-density length in the hippocampal CA1 region. These findings suggest that chewing during prenatal stress in dams could be an effective coping strategy to prevent hippocampal behavioral and morphologic impairments in their offspring.

  20. A new stress model, a scream sound, alters learning and monoamine levels in rat brain.

    PubMed

    Hu, Lili; Yang, Juan; Song, Tusheng; Hou, Ni; Liu, Yong; Zhao, Xiaoge; Zhang, Dianzeng; Wang, Lumin; Wang, Tao; Huang, Chen

    2014-01-17

    Most existing animal models for stress involve the simultaneous application of physical and psychological stress factors. In the current study, we described and used a novel psychological stress model (scream sound stress). To study the validity of it, we carried out acute and chronic scream sound stress. First, adult Sprague-Dawley (SD) rats were randomly divided into white noise, stress and background groups. The white noise group and stress group were treated with white noise and scream sound for 4h in the morning respectively. Compared with white noise and background groups, exposure to acute scream sound increased corticosterone (CORT) level and decreased latency in Morris water maze (MWM) test. The levels of noradrenaline (NE), dopamine (DA), 5-hydroxytryptamine (5-HT), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were altered in the striatum, hypothalamus and hippocampus of stress rats. Second, adult SD rats were randomly divided into background and stress groups, which were treated with scream sound for three weeks. Exposure to chronic scream sound suppressed body weight gain, increased corticosterone (CORT) level, influenced the morphology of adrenal gland, improved spleen and thymus indices, and decreased latency in MWM test. NE, DA, DOPAC, HVA and 5-HIAA levels were also altered in the brain of stress rats. Our results suggested that scream sound, as a novel stressor, facilitated learning ability, as well as altered monoamine levels in the rat brain. Moreover, scream sound is easy to apply and can be applied in more animals at the same time.

  1. Brain alterations in low-frequency fluctuations across multiple bands in obsessive compulsive disorder.

    PubMed

    Giménez, Mònica; Guinea-Izquierdo, Andrés; Villalta-Gil, Victoria; Martínez-Zalacaín, Ignacio; Segalàs, Cinto; Subirà, Marta; Real, Eva; Pujol, Jesús; Harrison, Ben J; Haro, Josep Maria; Sato, Joao R; Hoexter, Marcelo Q; Cardoner, Narcís; Alonso, Pino; Menchón, José Manuel; Soriano-Mas, Carles

    2016-10-22

    The extent of functional abnormalities in frontal-subcortical circuits in obsessive-compulsive disorder (OCD) is still unclear. Although neuroimaging studies, in general, and resting-state functional Magnetic Resonance Imaging (rs-fMRI), in particular, have provided relevant information regarding such alterations, rs-fMRI studies have been typically limited to the analysis of between-region functional connectivity alterations at low-frequency signal fluctuations (i.e., <0.08 Hz). Conversely, the local attributes of Blood Oxygen Level Dependent (BOLD) signal across different frequency bands have been seldom studied, although they may provide valuable information. Here, we evaluated local alterations in low-frequency fluctuations across different oscillation bands in OCD. Sixty-five OCD patients and 50 healthy controls underwent an rs-fMRI assessment. Alterations in the fractional amplitude of low-frequency fluctuations (fALFF) were evaluated, voxel-wise, across four different bands (from 0.01 Hz to 0.25 Hz). OCD patients showed decreased fALFF values in medial orbitofrontal regions and increased fALFF values in the dorsal-medial prefrontal cortex (DMPFC) at frequency bands <0.08 Hz. This pattern was reversed at higher frequencies, where increased fALFF values also appeared in medial temporal lobe structures and medial thalamus. Clinical variables (i.e., symptom-specific severities) were associated with fALFF values across the different frequency bands. Our findings provide novel evidence about the nature and regional distribution of functional alterations in OCD, which should contribute to refine neurobiological models of the disorder. We suggest that the evaluation of the local attributes of BOLD signal across different frequency bands may be a sensitive approach to further characterize brain functional alterations in psychiatric disorders.

  2. Neurobiological Alterations Induced by Exercise and Their Impact on Depressive Disorders

    PubMed Central

    Helmich, Ingo; Latini, Alexandra; Sigwalt, Andre; Carta, Mauro Giovanni; Machado, Sergio; Velasques, Bruna; Ribeiro, Pedro; Budde, Henning

    2010-01-01

    Background: The impact of physical activity on brain metabolic functions has been investigated in different studies and there is growing evidence that exercise can be used as a preventive and rehabilitative intervention in the treatment of depressive disorders. However, the exact neuronal mechanisms underlying the latter phenomenon have not been clearly elucidated. The present article summarises key results derived from studies that focussed on the neurobiological impact of exercise on brain metabolic functions associated with depressive disorders. Since major depressive disorder (MDD) is a life threatening disease it is of great significance to find reliable strategies to prevent or to cure this illness. Therefore, the aim of this paper is to review (1) the physiological relationship between physical activity and depressive disorders and (2) the potential neurobiological alterations induced by exercise that might lead to the relief of mental disorders like depression. Methods: We searched electronic databases for literature concerning the relationship between exercise and depression from 1963 until 2009. Results: The data suggests an association between physical inactivity and higher levels of depressive symptoms. Properly designed studies could show that exercise training can be as effective as antidepressive medications. Conclusion: The exact mechanisms how exercise affects the brain are not fully understood and the literature lacks of well designed studies concerning the effects of exercise training on depressive disorders. But the observed antidepressant actions of exercise are strong enough that it already can be used as an alternative to current medications in the treatment of depressive disorders. PMID:21283646

  3. Consistently altered expression of gene sets in postmortem brains of individuals with major psychiatric disorders

    PubMed Central

    Darby, M M; Yolken, R H; Sabunciyan, S

    2016-01-01

    The measurement of gene expression in postmortem brain is an important tool for understanding the pathogenesis of serious psychiatric disorders. We hypothesized that major molecular deficits associated with psychiatric disease would affect the entire brain, and such deficits may be shared across disorders. We performed RNA sequencing and quantified gene expression in the hippocampus of 100 brains in the Stanley Array Collection followed by replication in the orbitofrontal cortex of 57 brains in the Stanley Neuropathology Consortium. We then identified genes and canonical pathway gene sets with significantly altered expression in schizophrenia and bipolar disorder in the hippocampus and in schizophrenia, bipolar disorder and major depression in the orbitofrontal cortex. Although expression of individual genes varied, gene sets were significantly enriched in both of the brain regions, and many of these were consistent across diagnostic groups. Further examination of core gene sets with consistently increased or decreased expression in both of the brain regions and across target disorders revealed that ribosomal genes are overexpressed while genes involved in neuronal processes, GABAergic signaling, endocytosis and antigen processing have predominantly decreased expression in affected individuals compared to controls without a psychiatric disorder. Our results highlight pathways of central importance to psychiatric health and emphasize messenger RNA processing and protein synthesis as potential therapeutic targets for all three of the disorders. PMID:27622934

  4. Neurophysiological correlates of altered response inhibition in internet gaming disorder and obsessive-compulsive disorder: Perspectives from impulsivity and compulsivity.

    PubMed

    Kim, Minah; Lee, Tak Hyung; Choi, Jung-Seok; Kwak, Yoo Bin; Hwang, Wu Jeong; Kim, Taekwan; Lee, Ji Yoon; Lim, Jae-A; Park, Minkyung; Kim, Yeon Jin; Kim, Sung Nyun; Kim, Dai Jin; Kwon, Jun Soo

    2017-01-30

    Although internet gaming disorder (IGD) and obsessive-compulsive disorder (OCD) represent opposite ends of the impulsivity and compulsivity dimensions, the two disorders share common neurocognitive deficits in response inhibition. However, the similarities and differences in neurophysiological features of altered response inhibition between IGD and OCD have not been investigated sufficiently. In total, 27 patients with IGD, 24 patients with OCD, and 26 healthy control (HC) subjects participated in a Go/NoGo task with electroencephalographic recordings. N2-P3 complexes elicited during Go and NoGo condition were analyzed separately and compared among conditions and groups. NoGo-N2 latency at the central electrode site was delayed in IGD group versus the HC group and correlated positively with the severity of internet game addiction and impulsivity. NoGo-N2 amplitude at the frontal electrode site was smaller in OCD patients than in IGD patients. These findings suggest that prolonged NoGo-N2 latency may serve as a marker of trait impulsivity in IGD and reduced NoGo-N2 amplitude may be a differential neurophysiological feature between OCD from IGD with regard to compulsivity. We report the first differential neurophysiological correlate of the altered response inhibition in IGD and OCD, which may be a candidate biomarker for impulsivity and compulsivity.

  5. Neurophysiological correlates of altered response inhibition in internet gaming disorder and obsessive-compulsive disorder: Perspectives from impulsivity and compulsivity

    PubMed Central

    Kim, Minah; Lee, Tak Hyung; Choi, Jung-Seok; Kwak, Yoo Bin; Hwang, Wu Jeong; Kim, Taekwan; Lee, Ji Yoon; Lim, Jae-A; Park, Minkyung; Kim, Yeon Jin; Kim, Sung Nyun; Kim, Dai Jin; Kwon, Jun Soo

    2017-01-01

    Although internet gaming disorder (IGD) and obsessive-compulsive disorder (OCD) represent opposite ends of the impulsivity and compulsivity dimensions, the two disorders share common neurocognitive deficits in response inhibition. However, the similarities and differences in neurophysiological features of altered response inhibition between IGD and OCD have not been investigated sufficiently. In total, 27 patients with IGD, 24 patients with OCD, and 26 healthy control (HC) subjects participated in a Go/NoGo task with electroencephalographic recordings. N2-P3 complexes elicited during Go and NoGo condition were analyzed separately and compared among conditions and groups. NoGo-N2 latency at the central electrode site was delayed in IGD group versus the HC group and correlated positively with the severity of internet game addiction and impulsivity. NoGo-N2 amplitude at the frontal electrode site was smaller in OCD patients than in IGD patients. These findings suggest that prolonged NoGo-N2 latency may serve as a marker of trait impulsivity in IGD and reduced NoGo-N2 amplitude may be a differential neurophysiological feature between OCD from IGD with regard to compulsivity. We report the first differential neurophysiological correlate of the altered response inhibition in IGD and OCD, which may be a candidate biomarker for impulsivity and compulsivity. PMID:28134318

  6. Disorder specificity despite comorbidity: resting EEG alpha asymmetry in major depressive disorder and post-traumatic stress disorder.

    PubMed

    Kemp, A H; Griffiths, K; Felmingham, K L; Shankman, S A; Drinkenburg, W; Arns, M; Clark, C R; Bryant, R A

    2010-10-01

    The approach-withdrawal and valence-arousal models highlight that specific brain laterality profiles may distinguish depression and anxiety. However, studies remain to be conducted in multiple clinical populations that directly test the diagnostic specificity of these hypotheses. The current study compared electroencephalographic data under resting state, eyes closed conditions in patients with major depressive disorder (MDD) (N=15) and post-traumatic stress disorder (PTSD) (N=14) relative to healthy controls (N=15) to examine the specificity of brain laterality in these disorders. Key findings included (1) reduced left-frontal activity in MDD, (2) a positive correlation between PTSD severity and right-frontal lateralisation, (3) greater activity in PTSD patients relative to MDD within the right-parietotemporal region, and (4) globally increased alpha power in MDD. Findings partially support the diagnostic applicability of the theoretical frameworks. Future studies may benefit from examining task-driven differences between groups.

  7. Measuring the Quality of Care for Psychological Health Conditions in the Military Health System: Candidate Quality Measures for Posttraumatic Stress Disorder and Major Depressive Disorder

    DTIC Science & Technology

    2015-01-01

    Candidate Quality Measures for Posttraumatic Stress Disorder and Major Depressive Disorder C O R P O R A T I O N Report Documentation Page Form...Candidate Quality Measures for Posttraumatic Stress Disorder and Major Depressive Disorder 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT...stress disorder (PTSD) and major depressive disorder (MDD) ??? have become more common, with prevalence estimates up to 20 percent for PTSD and 37

  8. [Violence and post-traumatic stress disorder in childhood].

    PubMed

    Ximenes, Liana Furtado; de Oliveira, Raquel de Vasconcelos Carvalhães; de Assis, Simone Gonçalves

    2009-01-01

    This study presents the prevalence of symptoms of Posttraumatic Stress Disorder (PTSD) in 500 schoolchildren (6-13 years old) in São Gonçalo, Rio de Janeiro. It also investigates the association between PTSD, violence and other adverse events in the lives of these children. The multi-stage cluster sampling strategy involved three selection stages. Parents were interviewed about their children's behavior. The instrument used to screen symptoms of PTSD was the Child Behavior Checklist-Posttraumatic Stress Disorder Scale (CBCL-PTSD). Conflict Tactics Scales (CTS) were applied to evaluate family violence and other scales to investigate the socioeconomic profile, familiar relationship, characteristics and adverse events in the lives of the children. Multivariate analysis was performed using a hierarchical model with a significance level of 5%. The prevalence of clinical symptoms of PTSD was of 6.5%. The multivariate analysis suggested an explanation model of PTSD characterized by 18 variables, such as the child's characteristics; specific life events; family violence; and other family factors. The results reveal that it is necessary to work with the child in particularly difficult moments of his/her life in order to prevent or minimize the impact of adverse events on their mental and social functioning.

  9. Posttraumatic Stress Disorder: Does the Gut Microbiome Hold the Key?

    PubMed Central

    Leclercq, Sophie; Forsythe, Paul

    2016-01-01

    Gut bacteria strongly influence our metabolic, endocrine, immune, and both peripheral and central nervous systems. Microbiota do this directly and indirectly through their components, shed and secreted, ranging from fermented and digested dietary and host products to functionally active neurotransmitters including serotonin, dopamine, and γ-aminobutyric acid. Depression has been associated with enhanced levels of proinflammatory biomarkers and abnormal responses to stress. Posttraumatic stress disorder (PTSD) appears to be marked in addition by low cortisol responses, and these factors seem to predict and predispose individuals to develop PTSD after a traumatic event. Dysregulation of the immune system and of the hypothalamic-pituitary-adrenal axis observed in PTSD may reflect prior trauma exposure, especially early in life. Early life, including the prenatal period, is a critical time in rodents, and may well be for humans, for the functional and structural development of the immune and nervous systems. These, in turn, are likely shaped and programmed by gut and possibly other bacteria. Recent experimental and clinical data converge on the hypothesis that imbalanced gut microbiota in early life may have long-lasting immune and other physiologic effects that make individuals more susceptible to develop PTSD after a traumatic event and contribute to the disorder. This suggests that it may be possible to target abnormalities in these systems by manipulation of certain gut bacterial communities directly through supplementation or indirectly by dietary and other novel approaches. PMID:27254412

  10. Understanding posttraumatic stress disorder through fear conditioning, extinction and reconsolidation.

    PubMed

    Careaga, Mariella Bodemeier Loayza; Girardi, Carlos Eduardo Neves; Suchecki, Deborah

    2016-12-01

    Careaga MBL, Girardi CEN, Suchecki D. Understanding posttraumatic stress disorder through fear conditioning, extinction and reconsolidation. NEUROSCI BIOBEHAV REV -Posttraumatic stress disorder (PTSD) is a psychopathology characterized by exacerbation of fear response. A dysregulated fear response may be explained by dysfunctional learning and memory, a hypothesis that was proposed decades ago. A key component of PTSD is fear conditioning and the study of this phenomenon in laboratory has expanded the understanding of the underlying neurobiological changes in PTSD. Furthermore, traumatic memories are strongly present even years after the trauma and maintenance of this memory is usually related to behavioral and physiological maladaptive responses. Persistence of traumatic memory may be explained by a dysregulation of two memory processes: extinction and reconsolidation. The former may explain the over-expression of fear responses as an imbalance between traumatic and extinction memory. The latter, in turn, explains the maintenance of fear responses as a result of enhancing trauma-related memories. Thus, this review will discuss the importance of fear conditioning for the establishment of PTSD and how failure in extinction or abnormal reconsolidation may contribute to the maintenance of fear response overtime.

  11. Harm expectancy violation during exposure therapy for posttraumatic stress disorder.

    PubMed

    de Kleine, Rianne A; Hendriks, Lotte; Becker, Eni S; Broekman, Theo G; van Minnen, Agnes

    2017-03-31

    Exposure therapy has proven efficacy in the treatment of posttraumatic stress disorder (PTSD). Emotional processing theory proposes that fear habituation is a central mechanism in symptom reduction, but the empirical evidence supporting this is mixed. Recently it has been proposed that violation of harm expectancies is a crucial mechanism of action in exposure therapy. But to date, changes in harm expectancies have not been examined during exposure therapy in PTSD. The goal of the current study was to examine harm expectancy violation as mechanism of change in exposure therapy for posttraumatic stress disorder (PTSD). Patients (N=50, 44 female) with a primary diagnosis of chronic PTSD received intensive exposure therapy. Harm expectancies, harm experiences and subjective units of distress (SUDs) were assessed at each imaginal exposure session, and PTSD symptoms were assessed pre- and posttreatment with the Clinician Administered PTSD Scale (CAPS). Results showed that harm expectancies were violated within and strongly declined in-between exposure therapy sessions. However, expectancy violation was not related to PTSD symptom change. Fear habituation measures were moderately related to PTSD symptom reductions. In line with theory, exposure therapy promotes expectancy violation in PTSD patients, but this is not related to exposure therapy outcome. More work is warranted to investigate mechanisms of change during exposure therapy in PTSD.

  12. Attention Bias Variability and Symptoms of Posttraumatic Stress Disorder

    PubMed Central

    Murrough, James W.; Feder, Adriana; Fruchter, Eyal; Levinstein, Yoav; Wald, Ilan; Bailey, Christopher R.; Pine, Daniel S.; Neumeister, Alexander; Bar-Haim, Yair; Charney, Dennis S.

    2015-01-01

    Cognitive theories implicate information-processing biases in the etiology of anxiety disorders. Results of attention-bias studies in posttraumatic stress disorder (PTSD) have been inconsistent, suggesting biases towards and away from threat. Within-subject variability of attention biases in posttraumatic patients may be a useful marker for attentional control impairment and the development of posttrauma symptoms. This study reports 2 experiments investigating threat-related attention biases, mood and anxiety symptoms, and attention-bias variability following trauma. Experiment 1 included 3 groups in a cross-sectional design: (a) PTSD, (b) trauma-exposed without PTSD, and (c) healthy controls with no trauma or Axis I diagnoses. Greater attention-bias variability was found in the PTSD group compared to the other 2 groups (ηp2 = .23); attention-bias variability was significantly and positively correlated (r = .37) with PTSD symptoms. Experiment 2 evaluated combat-exposed and nonexposed soldiers before and during deployment. Attention-bias variability did not differentiate groups before deployment, but did differentiate groups during deployment (ηp2 = .16); increased variability was observed in groups with acute posttraumatic stress symptoms and acute depression symptoms only. Attention-bias variability could be a useful marker for attentional impairment related to threat cues associated with mood and anxiety symptoms after trauma exposure. PMID:24604631

  13. POSTTRAUMATIC STRESS DISORDER AND TRAUMA IN YOUTH IN JUVENILE DETENTION

    PubMed Central

    Abram, Karen M.; Teplin, Linda A.; Charles, Devon R.; Longworth, Sandra L.; McClelland, Gary M.; Dulcan, Mina K.

    2010-01-01

    Objective To determine prevalence estimates of exposure to trauma and 12-month rates of posttraumatic stress disorder (PTSD) among juvenile detainees by demographic subgroups (sex, race/ethnicity, and age). Design Epidemiologic study of juvenile detainees. Master’s level clinical research interviewers administered the posttraumatic stress disorder module of the Diagnostic Interview Schedule for Children (DISC-IV) to randomly selected detainees. Setting A large, temporary detention center for juveniles in Cook County, Illinois (which includes Chicago and surrounding suburbs). Participants Randomly selected, stratified sample of 898 African American, non-Hispanic white, and Hispanic youth (532 males, 366 females, ages 10–18) arrested and newly detained. Main Outcome Measures Diagnostic Interview Schedule for Children (DISC-IV). Results Most participants (92.5%) had experienced one or more traumas (mean = 14.6 incidents, median = 6 incidents). Significantly more males (93.2%) than females (84.0%) reported at least one traumatic experience; 11.2% of the sample met criteria for PTSD in the past year. Over half of the participants with PTSD reported witnessing violence as the precipitating trauma. Conclusion Trauma and PTSD appear to be more prevalent among juvenile detainees than in community samples. We recommend directions for research and discuss implications for mental health policy. PMID:15066899

  14. Post-traumatic stress disorder symptoms may explain poor mental health in patients with fibromyalgia.

    PubMed

    Toussaint, Loren L; Whipple, Mary O; Vincent, Ann

    2015-10-20

    Symptoms of post-traumatic stress disorder are common in fibromyalgia patients. This study compared post-traumatic stress disorder symptoms in fibromyalgia patients and healthy controls and determined whether patient-control differences in post-traumatic stress disorder symptoms mediated differences in mental health. In all, 30 patients and 30 healthy controls completed questionnaires assessing symptoms of post-traumatic stress disorder and mental health. Fibromyalgia patients had greater symptoms of post-traumatic stress disorder and mental health than controls. Patient-control differences in mental health symptoms were fully or partially mediated by differences in post-traumatic stress disorder symptoms. Healthcare providers should understand the role of trauma as management of trauma symptoms may be one strategy for improving mental health.

  15. Accelerated resolution therapy: an innovative mental health intervention to treat post-traumatic stress disorder.

    PubMed

    Finnegan, Alan; Kip, K; Hernandez, D; McGhee, S; Rosenzweig, L; Hynes, C; Thomas, M

    2016-04-01

    Post-traumatic stress disorder (PTSD) is a disabling trauma and stress-related disorder that may occur after a person experiences a traumatic event, and evokes a combination of intrusion and avoidance symptoms, negative alterations in cognitions and mood, and alterations in arousal and reactivity. Accelerated resolution therapy (ART) is an emerging psychotherapy that provides fast and lasting resolution for mental health problems such as PTSD. ART has been shown to achieve a positive result in one to five sessions, typically over a 2-week period, and requires no homework, skills practice or repeated exposure to targeted events. Initial research, including one randomised control trial, has demonstrated that ART interventions can significantly reduce symptoms of psychological trauma in both civilians and US service members and veterans. These results suggest that ART be considered as either a primary treatment option or for refractory PTSD in those with a suboptimal response to endorsed first-line therapies. Conservative estimates indicate substantial potential cost savings in PTSD treatment. Despite the need for more definitive clinical trials, there is increasing interest in ART in the USA, including in the US Army. The growing positive empirical evidence is compelling, and there appears to be sufficient evidence to warrant UK researchers undertaking ART research. The armed forces offer the potential for comparative international trials. However, equally important are veterans, emergency services personnel and those subjected to violence. ART appears to also have application in other conditions, including depression, anxiety disorders, and alcohol or drug misuse. ART can potentially help personnel traumatised by the unique challenges of war and conflict zones by providing brief psychotherapy in a readily accessible and culturally competent manner. ART facilitates the provision of interventions and resolutions in theatre, thus enhancing forces' fighting capability.

  16. Mild Traumatic Brain Injury with Social Defeat Stress Alters Anxiety, Contextual Fear Extinction, and Limbic Monoamines in Adult Rats

    PubMed Central

    Davies, Daniel R.; Olson, Dawne; Meyer, Danielle L.; Scholl, Jamie L.; Watt, Michael J.; Manzerra, Pasquale; Renner, Kenneth J.; Forster, Gina L.

    2016-01-01

    Mild traumatic brain injury (mTBI) produces symptoms similar to those typifying posttraumatic stress disorder (PTSD) in humans. We sought to determine whether a rodent model of stress concurrent with mTBI produces characteristics of PTSD such as impaired contextual fear extinction, while also examining concurrent alterations to limbic monoamine activity in brain regions relevant to fear and anxiety states. Male rats were exposed to social stress or control conditions immediately prior to mTBI induction, and 6 days later were tested either for anxiety-like behavior using the elevated plus maze (EPM), or for contextual fear conditioning and extinction. Brains were collected 24 h after EPM testing, and tissue from various limbic regions analyzed for content of monoamines, their precursors and metabolites using HPLC with electrochemical detection. Either social defeat or mTBI alone decreased time spent in open arms of the EPM, indicating greater anxiety-like behavior. However, this effect was enhanced by the combination of treatments. Further, rats exposed to both social defeat and mTBI exhibited greater freezing within extinction sessions compared to all other groups, suggesting impaired contextual fear extinction. Social defeat combined with mTBI also had greater effects on limbic monoamines than either insult alone, particularly with respect to serotonergic effects associated with anxiety and fear learning. The results suggest social stress concurrent with mTBI produces provides a relevant animal model for studying the prevention and treatment of post-concussive psychobiological outcomes. PMID:27147992

  17. Social Isolation Stress Induces Anxious-Depressive-Like Behavior and Alterations of Neuroplasticity-Related Genes in Adult Male Mice

    PubMed Central

    Ieraci, Alessandro; Mallei, Alessandra; Popoli, Maurizio

    2016-01-01

    Stress is a major risk factor in the onset of several neuropsychiatric disorders including anxiety and depression. Although several studies have shown that social isolation stress during postweaning period induces behavioral and brain molecular changes, the effects of social isolation on behavior during adulthood have been less characterized. Aim of this work was to investigate the relationship between the behavioral alterations and brain molecular changes induced by chronic social isolation stress in adult male mice. Plasma corticosterone levels and adrenal glands weight were also analyzed. Socially isolated (SI) mice showed higher locomotor activity, spent less time in the open field center, and displayed higher immobility time in the tail suspension test compared to group-housed (GH) mice. SI mice exhibited reduced plasma corticosterone levels and reduced difference between right and left adrenal glands. SI showed lower mRNA levels of the BDNF-7 splice variant, c-Fos, Arc, and Egr-1 in both hippocampus and prefrontal cortex compared to GH mice. Finally, SI mice exhibited selectively reduced mGluR1 and mGluR2 levels in the prefrontal cortex. Altogether, these results suggest that anxious- and depressive-like behavior induced by social isolation stress correlates with reduction of several neuroplasticity-related genes in the hippocampus and prefrontal cortex of adult male mice. PMID:26881124

  18. Social Isolation Stress Induces Anxious-Depressive-Like Behavior and Alterations of Neuroplasticity-Related Genes in Adult Male Mice.

    PubMed

    Ieraci, Alessandro; Mallei, Alessandra; Popoli, Maurizio

    2016-01-01

    Stress is a major risk factor in the onset of several neuropsychiatric disorders including anxiety and depression. Although several studies have shown that social isolation stress during postweaning period induces behavioral and brain molecular changes, the effects of social isolation on behavior during adulthood have been less characterized. Aim of this work was to investigate the relationship between the behavioral alterations and brain molecular changes induced by chronic social isolation stress in adult male mice. Plasma corticosterone levels and adrenal glands weight were also analyzed. Socially isolated (SI) mice showed higher locomotor activity, spent less time in the open field center, and displayed higher immobility time in the tail suspension test compared to group-housed (GH) mice. SI mice exhibited reduced plasma corticosterone levels and reduced difference between right and left adrenal glands. SI showed lower mRNA levels of the BDNF-7 splice variant, c-Fos, Arc, and Egr-1 in both hippocampus and prefrontal cortex compared to GH mice. Finally, SI mice exhibited selectively reduced mGluR1 and mGluR2 levels in the prefrontal cortex. Altogether, these results suggest that anxious- and depressive-like behavior induced by social isolation stress correlates with reduction of several neuroplasticity-related genes in the hippocampus and prefrontal cortex of adult male mice.

  19. Multicomponent Behavioral Treatment for Chronic Combat-Related Posttraumatic Stress Disorder: Trauma Management Therapy

    ERIC Educational Resources Information Center

    Turner, Samuel M.; Beidel, Deborah C.; Frueh, B. Christopher

    2005-01-01

    Posttraumatic stress disorder (PTSD) is a severe and chronic mental disorder that is highly prevalent within Veterans Affairs (VA) Medical Centers. A severe psychiatric disorder, combat-related PTSD is typically accompanied by multiple comorbid psychiatric disorders, symptom chronicity, and extreme social maladjustment. Thus, PTSD is a complex…

  20. Acute Heat Stress and Reduced Nutrient Intake Alter Intestinal Proteomic Profile and Gene Expression in Pigs

    PubMed Central

    Pearce, Sarah C.; Lonergan, Steven M.; Huff-Lonergan, Elisabeth; Baumgard, Lance H.; Gabler, Nicholas K.

    2015-01-01

    Heat stress and reduced feed intake negatively affect intestinal integrity and barrier function. Our objective was to compare ileum protein profiles of pigs subjected to 12 hours of HS, thermal neutral ad libitum feed intake, or pair-fed to heat stress feed intake under thermal neutral conditions (pair-fed thermal neutral). 2D-Differential In Gel Electrophoresis and gene expression were performed. Relative abundance of 281 and 138 spots differed due to heat stress, compared to thermal neutral and pair-fed thermal neutral pigs, respectively. However, only 20 proteins were different due to feed intake (thermal neutral versus pair-fed thermal neutral). Heat stress increased mRNA expression of heat shock proteins and protein abundance of heat shock proteins 27, 70, 90-α and β were also increased. Heat stress reduced ileum abundance of several metabolic enzymes, many of which are involved in the glycolytic or TCA pathways, indicating a change in metabolic priorities. Stress response enzymes peroxiredoxin-1 and peptidyl-prolyl cis-trans isomerase A were decreased in pair-fed thermal neutral and thermal neutral pigs compared to heat stress. Heat stress increased mRNA abundance markers of ileum hypoxia. Altogether, these data show that heat stress directly alters intestinal protein and mRNA profiles largely independent of reduced feed intake. These changes may be related to the reduced intestinal integrity associated with heat stress. PMID:26575181

  1. Restraint stress alters immune parameters and induces oxidative stress in the mouse uterus during embryo implantation.

    PubMed

    Liu, Guanhui; Dong, Yulan; Wang, Zixu; Cao, Jing; Chen, Yaoxing

    2014-12-01

    The influence of stress on embryo implantation is not well understood. Prior studies have focused on later gestational stages and the long-term impact of stress on immune function. The objective of this study is to investigate the effects of restraint stress on the immune parameters and the oxidative states of the uterus during implantation. In this study, pregnant CD1 mice were subjected to restraint stress (4 h/d) on embryonic day 1 (E1) and sacrificed on E3, E5, and E7. Maternal plasma corticosterone (CORT) secretion and implantation sites in the uterus were examined. The uterine (excluding embryos) homogenate and uterine lymphocytes were collected to examine oxidative stress states and associated immune parameters. The results demonstrated that restraint stress increased maternal plasma CORT secretion and reduced the number of implantation sites by 15.3% on E5 and by 26.1% on E7. Moreover, restraint stress decreased the density of uterine natural killer (uNK) cells in the endometrium by 22.1-47.9% and increased the density of mast cells in the myometrium by 55.6-76.9%. Restraint stress remarkably decreased the CD3(+)CD4(+) T/CD3(+)CD8(+) T cell ratio (by 26.2-28.9%) and attenuated uterine lymphocyte proliferation and secretion of cytokines. In addition, restraint stress threatened the intracellular equilibrium between oxidants and antioxidants, resulting in decreased glutathione peroxidase (GSH-PX) (32.2% and 45.7%), superoxide dismutase (SOD) (15.5% and 26.1%), and total antioxidant capacity (T-AOC) (18.4% and 18.2%) activities and increased malondialdehyde (MDA) (34.4% and 43.0%) contents on E5 and E7. In conclusion, these findings demonstrate that restraint stress causes abnormal implantation and negatively impacts immune parameters in association with oxidative stress in mice.

  2. Contrived motivating operations alter delay-discounting values of disordered gamblers.

    PubMed

    Dixon, Mark R; Buono, Frank D; Belisle, Jordan

    2016-12-01

    The present study required 9 disordered gamblers to make hypothetical selections between smaller and larger amounts of money at varying delays. Participants were also required to respond to the task given the contrived hypothetical conditions of earning twice or half as much as they did at their current jobs. The results demonstrated how participants' delay discounting was altered via contrived motivating operations, strengthening the argument that discounting may be a state variable.

  3. Telemedicine for Improved Delivery of Psychosocial Treatments for Post Traumatic Stress Disorder

    DTIC Science & Technology

    2014-05-01

    08-2-0076 TITLE: Telemedicine for Improved Delivery of Psychosocial Treatments for Post Traumatic Stress Disorder PRINCIPAL INVESTIGATOR...SUBTITLE Telemedicine for Improved Delivery of Psychosocial Treatments for Post-Traumatic Stress Disorder 5a. CONTRACT NUMBER 5b. GRANT...ABSTRACT: Background: Posttraumatic stress disorder (PTSD) is considered a major public health problem in the U.S. because it has fairly high prevalence

  4. Brain structure in post-traumatic stress disorder: A voxel-based morphometry analysis.

    PubMed

    Tan, Liwen; Zhang, Li; Qi, Rongfeng; Lu, Guangming; Li, Lingjiang; Liu, Jun; Li, Weihui

    2013-09-15

    This study compared the difference in brain structure in 12 mine disaster survivors with chronic post-traumatic stress disorder, 7 cases of improved post-traumatic stress disorder symptoms, and 14 controls who experienced the same mine disaster but did not suffer post-traumatic stress disorder, using the voxel-based morphometry method. The correlation between differences in brain structure and post-traumatic stress disorder symptoms was also investigated. Results showed that the gray matter volume was the highest in the trauma control group, followed by the symptoms-improved group, and the lowest in the chronic post-traumatic stress disorder group. Compared with the symptoms-improved group, the gray matter volume in the lingual gyrus of the right occipital lobe was reduced in the chronic post-traumatic stress disorder group. Compared with the trauma control group, the gray matter volume in the right middle occipital gyrus and left middle frontal gyrus was reduced in the symptoms-improved group. Compared with the trauma control group, the gray matter volume in the left superior parietal lobule and right superior frontal gyrus was reduced in the chronic post-traumatic stress disorder group. The gray matter volume in the left superior parietal lobule was significantly positively correlated with the State-Trait Anxiety Inventory subscale score in the symptoms-improved group and chronic post-traumatic stress disorder group (r = 0.477, P = 0.039). Our findings indicate that (1) chronic post-traumatic stress disorder patients have gray matter structural damage in the prefrontal lobe, occipital lobe, and parietal lobe, (2) after post-traumatic stress, the disorder symptoms are improved and gray matter structural damage is reduced, but cannot recover to the trauma-control level, and (3) the superior parietal lobule is possibly associated with chronic post-traumatic stress disorder. Post-traumatic stress disorder patients exhibit gray matter abnormalities.

  5. Alterations of Lipid-Lipoprotein and Leptin in Bipolar Disorder Associated with Clinic Process

    PubMed Central

    BÜLBÜL, Feridun; ERYİĞİT, Ayşegül Giray; ERBAĞCI, A. Binnur; SELEK, Salih; SAVAŞ, Haluk

    2014-01-01

    Introduction Obesity is more common among patients with bipolar disorder as compared to normal population. There are studies showing increased leptin levels in obese patients. The aim of the present study was to investigate the alterations in leptin levels, body mass index (BMI), and lipid-lipoprotein levels during manic period, as well as during euthymic period, after one month in patients with bipolar disorder. Methods Thirty-one adult patients, who had been hospitalized in the psychiatry clinic because of manic period of bipolar disorder, were included in the present study. Serum leptin and lipid-lipoprotein levels and BMI of the patients were analyzed both on the first day and 30th day of hospitalization after they became euthymic. Results Total cholesterol and triglyceride levels significantly increased in male patients (p<.05). The increase in total cholesterol and LDL-C levels was not significant in female patients (p=.066 and p=.056, respectively). BMI was significantly, but slightly increased in both genders (.56±.14 kg/m2), however, such a change was not observed in serum leptin levels. Conclusion Results of the present study demonstrated that clinical improvement in bipolar patients showed different association in each gender with the alterations in BMI and serum lipid and/or lipoprotein levels. Such an alteration might have resulted from direct or indirect effect of drugs, as well as from lifestyle changes.

  6. Early life stress alters pituitary growth during adolescence-a longitudinal study.

    PubMed

    Ganella, Despina E; Allen, Nicholas B; Simmons, Julian G; Schwartz, Orli; Kim, Jee Hyun; Sheeber, Lisa; Whittle, Sarah

    2015-03-01

    The pituitary gland is integral in mediating the stress-response via its role in hypothalamic-pituitary-adrenal (HPA) axis function. Pituitary gland volume (PGV) is altered in stress-related psychopathology, and one study to date has shown stress to be associated with age-related PGV change during adolescence. The current study investigated the effects of a number of different types of early life (i.e., childhood and adolescent) stress (including childhood maltreatment, stressful life events, and maternal affective behavior) on PGV development from mid- to late adolescence using a longitudinal design. The influence of PGV development on depressive and anxiety symptoms was also investigated. Ninety one (49 male) adolescents took part in mother-child dyadic interaction tasks when they were approximately 12 years old, reported on childhood maltreatment and stressful life events when they were approximately 15 years old, and underwent two waves of structural magnetic resonance imaging (MRI) scans, when they were approximately 16 and 19 years old. Results revealed that childhood maltreatment predicted accelerated PGV development in females, and maternal dysphoric behavior predicted accelerated PGV development in the whole sample. PGV development was not associated with depressive or anxiety symptoms. These results suggest an effect of early life stress on altered HPA axis function across mid- to late adolescence. Further research is required to assess functional implications and whether these changes might be associated with risk for subsequent psychopathology.

  7. Adolescence, Stress and Cortisol in Autism Spectrum Disorders

    PubMed Central

    Corbett, Blythe A.; Simon, David

    2014-01-01

    Adolescence, the transition between childhood and adulthood, is a period of remarkable physiological, psychological and social change. A variety of physiological changes coincide with the dynamic transition, which is evident in the regulation and responsivity of the Limbic-Hypothalamic-Pituitary-Adrenocortical (LHPA) axis. Specifically, elevations in diurnal basal cortisol levels have been reported, as well as higher cortisol in response to perceived stressors. While this enhanced responsivity may help prepare the individual to adapt to increased demands and new challenges, it may also mark a time of increased vulnerability in populations already prone to enhanced physiological arousal and poor adaption to change, such as autism. To date most studies investigating the integrity of the LHPA axis in children with autism spectrum disorders (ASD) have shown more variable diurnal regulation and a pattern of enhanced responsivity to stress. There is also evidence of more marked reactivity over development suggesting that adolescence may be a time of increased risk for enhanced physiological arousal and social stress. The following review briefly summarizes the literature to date on autism, adolescence and salivary cortisol. The current summary suggests that enhanced study of the interplay between social functioning and stress during the adolescent period in ASD is warranted. PMID:24665363

  8. Serotonin transporter polymorphism in major depressive disorder (MDD), psychiatric disorders, and in MDD in response to stressful life events: causes and treatment with antidepressant.

    PubMed

    Daniele, Antonella; Divella, Rosa; Paradiso, Angelo; Mattioli, Vittorio; Romito, Francesca; Giotta, Francesco; Casamassima, Porzia; Quaranta, Michele

    2011-01-01

    A functional polymorphism in the promoter region of the 5-hidroxytryptamine transporter gene (5-HTTLPR), alters its transcription. Short allele (SS) variation decreases the transcriptional efficacy of serotonin, causing psychiatric disorders, major depressive disorder (MDD) and major depression in response to stressful life events. The aim of this study was to determine the current understanding of the role of 5-HTTLPR polymorphism in the development of depressive episodes and its response to treatment. Twenty-five articles were identified from PubMed, utilizing the following keyword, 5-HTT transporter gene, polymorphism, depression, stressful condition, psychiatric disorder. All articles were read and notes were made regarding study participant, measures, data analysis and results, and were used to write this review. The distribution of the SS allele in patients is associated with an increased risk of MDD following exposure to stressful events of life. Additionally, this genetic variant is closely associated with several psychiatric conditions such as suicidal behaviour, psychoses, personality disorders, and aggressive-impulsive traits.

  9. White matter alterations in adults with probable developmental coordination disorder: an MRI diffusion tensor imaging study.

    PubMed

    Williams, Jacqueline; Kashuk, Saman R; Wilson, Peter H; Thorpe, Graham; Egan, Gary F

    2017-01-18

    Movement skill difficulties in children [or developmental coordination disorder (DCD)] often persist into adulthood (in up to 70% of cases). The suggestion of white matter microstructure alterations in children with DCD raises the question of whether similar alterations are present in adults with probable DCD (pDCD). Twelve adults with pDCD and 11 adults without pDCD underwent diffusion tensor imaging. The results showed that the pDCD group had significantly lower fractional anisotropy in the corticospinal tract and superior longitudinal fasciculus and lower mean diffusivity in the internal capsule and inferior longitudinal fasciculus. This suggests reduced white matter integrity in parietofrontal and corticospinal tracts, with possible compensatory increases in white matter integrity along the visual ventral stream and front-occipital networks. These findings support recent neuroimaging studies in children with DCD and suggest persistent neurobiological alterations along white matter tracts that are known to support motor planning, cognition and their association.

  10. High self-perceived stress and poor coping in intellectually able adults with autism spectrum disorder.

    PubMed

    Hirvikoski, Tatja; Blomqvist, My

    2015-08-01

    Despite average intellectual capacity, autistic traits may complicate performance in many everyday situations, thus leading to stress. This study focuses on stress in everyday life in intellectually able adults with autism spectrum disorders. In total, 53 adults (25 with autism spectrum disorder and 28 typical adults from the general population) completed the Perceived Stress Scale. Autistic traits were assessed using the Autism Spectrum Quotient. Adults with autism spectrum disorder reported significantly higher subjective stress and poorer ability to cope with stress in everyday life, as compared to typical adults. Autistic traits were associated with both subjective stress/distress and coping in this cross-sectional series. The long-term consequences of chronic stress in everyday life, as well as treatment intervention focusing on stress and coping, should be addressed in future research as well as in the clinical management of intellectually able adults with autism spectrum disorder.

  11. Nosema ceranae alters a highly conserved hormonal stress pathway in honeybees.

    PubMed

    Mayack, C; Natsopoulou, M E; McMahon, D P

    2015-12-01

    Nosema ceranae, an emerging pathogen of the western honeybee (Apis mellifera), is implicated in recent pollinator losses and causes severe energetic stress. However, whether precocious foraging and accelerated behavioural maturation in infected bees are caused by the infection itself or via indirect energetic stress remains unknown. Using a combination of nutritional and infection treatments, we investigated how starvation and infection alters the regulation of adipokinetic hormone (AKH) and octopamine, two highly conserved physiological pathways that respond to energetic stress by mobilizing fat stores and increasing search activity for food. Although there was no response from AKH when bees were experimentally infected with N. ceranae or starved, supporting the notion that honeybees have lost this pathway, there were significant regulatory changes in the octopamine pathway. Significantly, we found no evidence of acute energetic stress being the only cause of symptoms associated with N. ceranae infection. Therefore, the parasite itself appears to alter regulatory components along a highly conserved physiological pathway in an infection-specific manner. This indicates that pathogen-induced behavioural alteration of chronically infected bees should not just be viewed as a coincidental short-term by-product of pathogenesis (acute energetic stress) and may be a result of a generalist manipulation strategy to obtain energy for reproduction.

  12. Posttraumatic oxytocin dysregulation: Is it a link among posttraumatic self disorders, posttraumatic stress disorder, and pelvicvisceral dysregulation conditions in women?

    PubMed Central

    Seng, Julia S.

    2010-01-01

    This paper explicates a theory that oxytocin, a sexually dimorphic neurotransmitter and paracrine hormone, is a plausible mechanism linking early relational trauma with posttraumatic self disorders (e.g., dissociation, somatization, and interpersonal sensitivity), posttraumatic stress disorder per se and pelvicvisceral dysregulationdisorders (e.g., irritable bowel syndrome, chronic pelvic pain, interstitial cystitis, and hyperemesis gravidarum). This Posttraumatic Oxytocin Dysregulation Disorders theory is consistent with historic and contemporary literature. It integrates attention to psychological and physical comorbidities and could account for the increased incidence of these disorders among females. Specific propositions are explored in data from studies of traumatic stress and women's health. PMID:20938865

  13. Are Extremes of Consumption in Eating Disorders Related to an Altered Balance between Reward and Inhibition?

    PubMed Central

    Wierenga, Christina E.; Ely, Alice; Bischoff-Grethe, Amanda; Bailer, Ursula F.; Simmons, Alan N.; Kaye, Walter H.

    2014-01-01

    The primary defining characteristic of a diagnosis of an eating disorder (ED) is the “disturbance of eating or eating-related behavior that results in the altered consumption or absorption of food” (DSM V; American Psychiatric Association, 2013). There is a spectrum, ranging from those who severely restrict eating and become emaciated on one end to those who binge and overconsume, usually accompanied by some form of compensatory behaviors, on the other. How can we understand reasons for such extremes of food consummatory behaviors? Recent work on obesity and substance use disorders has identified behaviors and neural pathways that play a powerful role in human consummatory behaviors. That is, corticostriatal limbic and dorsal cognitive neural circuitry can make drugs and food rewarding, but also engage self-control mechanisms that may inhibit their use. Importantly, there is considerable evidence that alterations of these systems also occur in ED. This paper explores the hypothesis that an altered balance of reward and inhibition contributes to altered extremes of response to salient stimuli, such as food. We will review recent studies that show altered sensitivity to reward and punishment in ED, with evidence of altered activity in corticostriatal and insula processes with respect to monetary gains or losses, and tastes of palatable foods. We will also discuss evidence for a spectrum of extremes of inhibition and dysregulation behaviors in ED supported by studies suggesting that this is related to top-down self-control mechanisms. The lack of a mechanistic understanding of ED has thwarted efforts for evidence-based approaches to develop interventions. Understanding how ED behavior is encoded in neural circuits would provide a foundation for developing more specific and effective treatment approaches. PMID:25538579

  14. Repeated exposure of adult rats to transient oxidative stress induces various long-lasting alterations in cognitive and behavioral functions.

    PubMed

    Iguchi, Yoshio; Kosugi, Sakurako; Nishikawa, Hiromi; Lin, Ziqiao; Minabe, Yoshio; Toda, Shigenobu

    2014-01-01

    Exposure of neonates to oxidative stress may increase the risk of psychiatric disorders such as schizophrenia in adulthood. However, the effects of moderate oxidative stress on the adult brain are not completely understood. To address this issue, we systemically administrated 2-cyclohexen-1-one (CHX) to adult rats to transiently reduce glutathione levels. Repeated administration of CHX did not affect the acquisition or motivation of an appetitive instrumental behavior (lever pressing) rewarded by a food outcome under a progressive ratio schedule. In addition, response discrimination and reversal learning were not affected. However, acute CHX administration blunted the sensitivity of the instrumental performance to outcome devaluation, and this effect was prolonged in rats with a history of repeated CHX exposure, representing pro-depression-like phenotypes. On the other hand, repeated CHX administration reduced immobility in forced swimming tests and blunted acute cocaine-induced behaviors, implicating antidepressant-like effects. Multivariate analyses segregated a characteristic group of behavioral variables influenced by repeated CHX administration. Taken together, these findings suggest that repeated administration of CHX to adult rats did not cause a specific mental disorder, but it induced long-term alterations in behavioral and cognitive functions, possibly related to specific neural correlates.

  15. Stress-induced alterations of left-right electrodermal activity coupling indexed by pointwise transinformation.

    PubMed

    Světlák, M; Bob, P; Roman, R; Ježek, S; Damborská, A; Chládek, J; Shaw, D J; Kukleta, M

    2013-01-01

    In this study, we tested the hypothesis that experimental stress induces a specific change of left-right electrodermal activity (EDA) coupling pattern, as indexed by pointwise transinformation (PTI). Further, we hypothesized that this change is associated with scores on psychometric measures of the chronic stress-related psychopathology. Ninety-nine university students underwent bilateral measurement of EDA during rest and stress-inducing Stroop test and completed a battery of self-report measures of chronic stress-related psychopathology. A significant decrease in the mean PTI value was the prevalent response to the stress conditions. No association between chronic stress and PTI was found. Raw scores of psychometric measures of stress-related psychopathology had no effect on either the resting levels of PTI or the amount of stress-induced PTI change. In summary, acute stress alters the level of coupling pattern of cortico-autonomic influences on the left and right sympathetic pathways to the palmar sweat glands. Different results obtained using the PTI, EDA laterality coefficient, and skin conductance level also show that the PTI algorithm represents a new analytical approach to EDA asymmetry description.

  16. Distinctive transcriptome alterations of prefrontal pyramidal neurons in schizophrenia and schizoaffective disorder

    PubMed Central

    Arion, Dominique; Corradi, John P.; Tang, Shaowu; Datta, Dibyadeep; Boothe, Franklyn; He, Aiqing; Cacace, Angela M.; Zaczek, Robert; Albright, Charles F.; Tseng, George; Lewis, David A.

    2014-01-01

    Schizophrenia is associated with alterations in working memory that reflect dysfunction of dorsolateral prefrontal cortex (DLPFC) circuitry. Working memory depends on the activity of excitatory pyramidal cells in DLPFC layer 3, and to a lesser extent in layer 5. Although many studies have profiled gene expression in DLPFC gray matter in schizophrenia, little is known about cell type-specific transcript expression in these two populations of pyramidal cells. We hypothesized that interrogating gene expression specifically in DLPFC layer 3 or 5 pyramidal cells would reveal new and/or more robust schizophrenia-associated differences that would provide new insights into the nature of pyramidal cell dysfunction in the illness. We also sought to determine the impact of other variables, such as a diagnosis of schizoaffective disorder or medication use at time of death, on the patterns of gene expression in pyramidal neurons. Individual pyramidal cells in DLPFC layers 3 or 5 were captured by laser microdissection from 36 subjects with schizophrenia or schizoaffective disorder and matched normal comparison subjects. The mRNA from cell collections was subjected to transcriptome profiling by microarray followed by qPCR validation. Expression of genes involved in mitochondrial (MT) or ubiquitin-proteasome system (UPS) functions were markedly down-regulated in the patient group (p values for MT-related and UPS-related pathways were <10−7 and <10−5 respectively). MT-related gene alterations were more prominent in layer 3 pyramidal cells, whereas UPS-related gene alterations were more prominent in layer 5 pyramidal cells. Many of these alterations were not present, or found to a lesser degree, in samples of DLPFC gray matter from the same subjects, suggesting that they are pyramidal cell-specific. Furthermore, these findings principally reflected alterations in the schizophrenia subjects, were not present or present to a lesser degree in the schizoaffective disorder subjects

  17. Psychological treatments for concurrent posttraumatic stress disorder and substance use disorder: a systematic review.

    PubMed

    van Dam, Debora; Vedel, Ellen; Ehring, Thomas; Emmelkamp, Paul M G

    2012-04-01

    This article gives an overview of research into psychological treatments for concurrent posttraumatic stress disorder (PTSD) and substance used disorder (SUD), with a special focus on the effectiveness of treatments addressing both disorders compared to treatments addressing one of the disorders alone. In addition, a distinction is made between trauma-focused versus non-trauma-focused therapies for concurrent PTSD and SUD. The databases Embase, Psychinfo, Medline and Web of science were searched for relevant articles. In total, seventeen studies were identified evaluating ten treatments protocols (six trauma-focused and four non-trauma-focused treatment approaches). In general, the studies showed pre-post reductions for PTSD and/or SUD symptoms. Although most treatments for concurrent PTSD and SUD did not prove to be superior to regular SUD treatments, there are some promising preliminary results suggesting that some patients might benefit from trauma-focused interventions. However, the lack of methodologically sound treatment trials makes it difficult to draw firm conclusions. Methodological limitations are discussed, along with recommendations for future research.

  18. Sleep-disordered breathing in patients with post-traumatic stress disorder.

    PubMed

    Jaoude, Philippe; Vermont, Leah N; Porhomayon, Jahan; El-Solh, Ali A

    2015-02-01

    Post-traumatic stress disorder (PTSD) and sleep-disordered breathing (SDB) are shared by many patients. They both affect sleep and the quality of life of affected subjects. A critical review of the literature supports an association between the two disorders in both combat-related and non-combat-related PTSD. The exact mechanism linking PTSD and SDB is not fully understood. A complex interplay between sleep fragmentation and neuroendocrine pathways is suggested. The overlap of symptoms between PTSD and SDB raises diagnostic challenges that may require a novel approach in the methods used to diagnose the coexisting disorders. Similar therapeutic challenges face patients and providers when treating concomitant PTSD and SDB. Although continuous positive airway pressure therapy imparts a mitigating effect on PTSD symptomatology, lack of both acceptance and adherence are common. Future research should focus on ways to improve adherence to continuous positive airway pressure therapy and on the use of alternative therapeutic methods for treating SDB in patients with PTSD.

  19. Expression of oxidative stress-response genes is not activated in the prefrontal cortex of patients with depressive disorder.

    PubMed

    Teyssier, Jean-Raymond; Ragot, Sylviane; Chauvet-Gélinier, Jean-Christophe; Trojak, Benoit; Bonin, Bernard

    2011-04-30

    To test the hypothesis that the oxidative stress consistently detected in the peripheral blood of patients with depressive disorder impacts on the functionally relevant brain region, the expression level of nine major genes of the stress response and repair systems has been quantified in the prefrontal cortex of 24 depressive and 12 control subjects. These genes were: superoxide dismutase (SOD1), SOD2, catalase (CAT), gluthatione peroxidase 1 (GPx1), 8-oxoguanine DNA glycosylase (OGG1), nei-like 1 (NEIL1), methionine sulphoxide reductase A (MSRA), telomere repeat-binding factor 2 (TERF2) and C-FOS. Telomere length (a maker of chronic exposure to oxidative stress) has been measured in the DNA of the occipital cortex. No significant difference has been found between the compared groups. It must be concluded that the pathogenic role of the oxidative stress in the cerebral mechanism of depression cannot be inferred from the alteration of peripheral parameters.

  20. A large-scale perspective on stress-induced alterations in resting-state networks

    NASA Astrophysics Data System (ADS)

    Maron-Katz, Adi; Vaisvaser, Sharon; Lin, Tamar; Hendler, Talma; Shamir, Ron

    2016-02-01

    Stress is known to induce large-scale neural modulations. However, its neural effect once the stressor is removed and how it relates to subjective experience are not fully understood. Here we used a statistically sound data-driven approach to investigate alterations in large-scale resting-state functional connectivity (rsFC) induced by acute social stress. We compared rsfMRI profiles of 57 healthy male subjects before and after stress induction. Using a parcellation-based univariate statistical analysis, we identified a large-scale rsFC change, involving 490 parcel-pairs. Aiming to characterize this change, we employed statistical enrichment analysis, identifying anatomic structures that were significantly interconnected by these pairs. This analysis revealed strengthening of thalamo-cortical connectivity and weakening of cross-hemispheral parieto-temporal connectivity. These alterations were further found to be associated with change in subjective stress reports. Integrating report-based information on stress sustainment 20 minutes post induction, revealed a single significant rsFC change between the right amygdala and the precuneus, which inversely correlated with the level of subjective recovery. Our study demonstrates the value of enrichment analysis for exploring large-scale network reorganization patterns, and provides new insight on stress-induced neural modulations and their relation to subjective experience.

  1. Chicoric acid regulates behavioral and biochemical alterations induced by chronic stress in experimental Swiss albino mice.

    PubMed

    Kour, Kiranjeet; Bani, Sarang

    2011-09-01

    The present study was taken up to see the effect of chicoric acid (CA) on behavioral and biochemical alterations induced by chronic restraint stress in experimental Swiss albino mice. CA at 1mg/kg dose level exhibited considerable antidepressant activity as shown by significant decrease in immobility period in the Porsolt's swim stress-induced behavioral despair test and escape failures in Learned "helplessness test". The antidepressant activity shown by CA can be attributed to its modulating effect on nor-adrenaline (NA), dopamine (DA) and 5- hydroxy tryptamine (5-HT) as shown by their quantification in CA treated chronically stressed mice. Further, a significant antioxidant effect was exhibited by CA as shown by estimation of lipid peroxidation, glutathione (GSH) and glycogen in liver of chronically stressed mice. It also normalized altered values of serum glucose, triglycerides, aspartate aminotransferase (AST) alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in a dose dependent manner. The stress busting potential of CA was further confirmed by its regulating effect on raised plasma corticosterone levels and significant attenuation of the depleted ascorbic acid, cholesterol and corticosterone levels in adrenal glands. Thus, our results suggest that CA possesses considerable stress busting potential, and that anti-oxidation may be one of the mechanisms underlying its antistress action.

  2. Posterior Structural Brain Volumes Differ in Maltreated Youth with and without Chronic Posttraumatic Stress Disorder

    PubMed Central

    Bellis, Michael D. De; Hooper, Stephen R.; Chen, Steven D.; Provenzale, James M.; Boyd, Brian D.; Glessner, Christopher E.; MacFall, James R.; Payne, Martha E.; Rybczynski, Robert; Woolley, Donald P

    2016-01-01

    Magnetic resonance imaging (MRI) studies of maltreated children with posttraumatic stress disorder (PTSD) suggest that maltreatment-related PTSD is associated with adverse brain development. Maltreated youth resilient to chronic PTSD were not previously investigated and may elucidate neuro-mechanisms of the stress diathesis that leads to resilience to chronic PTSD. In this cross-sectional study, anatomical volumetric and corpus callosum diffusion tensor imaging measures were examined using MRI in maltreated youth with chronic PTSD (N=38), without PTSD (N=35), and non-maltreated participants (n=59). Groups were sociodemographically similar. Participants underwent assessments for strict inclusion/exclusion criteria and psychopathology. Maltreated youth with PTSD were psychobiologically different from maltreated youth without PTSD and non-maltreated controls. Maltreated youth with PTSD had smaller posterior cerebral and cerebellar gray matter volumes than maltreated youth without PTSD and non-maltreated participants. Cerebral and cerebellar gray matter volumes inversely correlated with PTSD symptoms. Posterior corpus callosum microstructure in pediatric maltreatment-related PTSD differed compared to maltreated youth without PTSD and controls. The group differences remained significant when controlling for psychopathology, numbers of Axis I disorders, and trauma load. Alterations of these posterior brain structures may result from a shared trauma related-mechanism or an inherent vulnerability that mediates the pathway from chronic PTSD to co-morbidity. PMID:26535944

  3. Post-traumatic Stress Disorder and Cardiovascular Disease.

    PubMed

    Burg, Matthew M; Soufer, Robert

    2016-10-01

    Post-traumatic stress disorder (PTSD) is a disabling condition that develops consequent to trauma exposure such as natural disasters, sexual assault, automobile accidents, and combat that independently increases risk for early incident cardiovascular disease (CVD) and cardiovascular (CV) mortality by over 50 % and incident hypertension risk by over 30 %. While the majority of research on PTSD and CVD has concerned initially healthy civilian and military veteran samples, emerging research is also demonstrating that PTSD consequent to the trauma of an acute cardiac event significantly increases risk for early recurrence and mortality and that patient experiences in the clinical pathway that are related to the emergency department environment may provide an opportunity to prevent PTSD onset and thus improve outcomes. Future directions for clinical and implementation science concern broad PTSD and trauma screening in the context of primary care medical environments and the testing of PTSD treatments with CVD-related surrogates and endpoints.

  4. Post-traumatic stress disorder: emerging concepts of pharmacotherapy.

    PubMed

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

    2009-06-01

    Post-traumatic 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.

  5. Pathways to suicidal behavior in posttraumatic stress disorder.

    PubMed

    Panagioti, Maria; Gooding, Patricia A; Dunn, Graham; Tarrier, Nicholas

    2011-04-01

    This study investigated paths to suicidal behavior in 94 civilian participants with chronic posttraumatic stress disorder (PTSD). Two statistical modeling programs, TETRAD II version 2.1 and Mplus 5.21 were used to construct a working model of suicide in PTSD. Two paths to suicidal behavior were identified. In the first path, suicidal behavior was directly associated with greater life impairment, which in turn was associated with poorer occupational and social functioning. In the second path, suicidal behavior was directly associated with depressive symptoms, which in turn were associated with more severe PTSD symptoms. Psychotropic medication, employment status, and threat to life further contributed to the model. The findings suggest that negative perceptions of functional impairment and depression are strongly associated with suicidal behavior in PTSD.

  6. The aftermath of violence: children, disaster, and posttraumatic stress disorder.

    PubMed

    Veenema, Tener Goodwin; Schroeder-Bruce, Kathryn

    2002-01-01

    Terrorist attacks, situations of armed conflict, and all forms of catastrophe tax our abilities to cope, understand, and respond. Because of their developmental status, children are even more emotionally vulnerable to the devastating effects of a disaster. When tragedy strikes a family, community, or the nation, helping children cope and regain a sense of safety is critical. A child with posttraumatic stress disorder (PTSD) develops symptoms such as intense fear, disorganized and agitated behavior, emotional numbness, anxiety, or depression after being directly exposed to or witnessing an extreme traumatic situation involving threatened death or serious injury. Victims of repeated abuse or children who live in violent neighborhoods or war zones, or who have witnessed extensive media coverage of violent events, may experience PTSD.

  7. Mindfulness meditation training alters stress-related amygdala resting state functional connectivity: a randomized controlled trial.

    PubMed

    Taren, Adrienne A; Gianaros, Peter J; Greco, Carol M; Lindsay, Emily K; Fairgrieve, April; Brown, Kirk Warren; Rosen, Rhonda K; Ferris, Jennifer L; Julson, Erica; Marsland, Anna L; Bursley, James K; Ramsburg, Jared; Creswell, J David

    2015-12-01

    Recent studies indicate that mindfulness meditation training interventions reduce stress and improve stress-related health outcomes, but the neural pathways for these effects are unknown. The present research evaluates whether mindfulness meditation training alters resting state functional connectivity (rsFC) of the amygdala, a region known to coordinate stress processing and physiological stress responses. We show in an initial discovery study that higher perceived stress over the past month is associated with greater bilateral amygdala-subgenual anterior cingulate cortex (sgACC) rsFC in a sample of community adults (n = 130). A follow-up, single-blind randomized controlled trial shows that a 3-day intensive mindfulness meditation training intervention (relative to a well-matched 3-day relaxation training intervention without a mindfulness component) reduced right amygdala-sgACC rsFC in a sample of stressed unemployed community adults (n = 35). Although stress may increase amygdala-sgACC rsFC, brief training in mindfulness meditation could reverse these effects. This work provides an initial indication that mindfulness meditation training promotes functional neuroplastic changes, suggesting an amygdala-sgACC pathway for stress reduction effects.

  8. Trauma Exposure and Posttraumatic Stress Disorder in the Canadian Military

    PubMed Central

    Brunet, Alain; Monson, Eva; Liu, Aihua; Fikretoglu, Deniz

    2015-01-01

    Objective: To estimate the lifetime prevalence of trauma exposure and posttraumatic stress disorder (PTSD) among a representative, active military sample, and to identify demographic and military variables that modulate rates of trauma exposure as well as PTSD rates and duration. Method: A cross-sectional weighted sample of 5155 regular members and 3957 reservists (n = 8441) of the Canadian Armed Forces (CAF) was face-to-face interviewed using a lay-administered structured interview that generates Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, psychiatric diagnoses. Results: Within this sample, 85.6% reported 1 or more trauma exposure, with a median number of 3 or more exposures. Compared with males, females were less likely (P < 0.05) to be exposed to warlike trauma (adjusted odds ratio [AOR] 0.40), disasters (AOR 0.43), assaultive violence (AOR 0.52), and witnessing trauma (AOR 0.75). However, they were more likely to report sexual assault (AOR 7.36). The lifetime prevalence of PTSD was 6.6% and the conditional rate was 7.7%. Both lifetime and conditional PTSD rates were higher among female soldiers, but lower among the reserve forces, both male and female. Finally, the median duration of PTSD was negatively influenced by younger age of onset, but not influenced by whether the event occurred during deployment. Conclusions: Active members of the CAF report a high degree of trauma exposure but a moderate rate of lifetime PTSD. PMID:26720506

  9. Latent Factor Structure of DSM-5 Posttraumatic Stress Disorder.

    PubMed

    Gentes, Emily; Dennis, Paul A; Kimbrel, Nathan A; Kirby, Angela C; Hair, Lauren P; Beckham, Jean C; Calhoun, Patrick S

    The current study examined the latent factor structure of posttraumatic stress disorder (PTSD) based on DSM-5 criteria in a sample of participants (N = 374) recruited for studies on trauma and health. Confirmatory factor analyses (CFA) were used to compare the fit of the previous 3-factor DSM-IV model of PTSD to the 4-factor model specified in DSM-5 as well as to a competing 4-factor "dysphoria" model (Simms, Watson, & Doebbeling, 2002) and a 5-factor (Elhai et al., 2011) model of PTSD. Results indicated that the Elhai 5-factor model (re-experiencing, active avoidance, emotional numbing, dysphoric arousal, anxious arousal) provided the best fit to the data, although substantial support was demonstrated for the DSM-5 4-factor model. Low factor loadings were noted for two of the symptoms in the DSM-5 model (psychogenic amnesia and reckless/self-destructive behavior), which raises questions regarding the adequacy of fit of these symptoms with other core features of the disorder. Overall, the findings from the present research suggest the DSM-5 model of PTSD is a significant improvement over the previous DSM-IV model of PTSD.

  10. Posttraumatic Stress Disorder Following the September 11, 2001, Terrorist Attacks

    PubMed Central

    Neria, Yuval; DiGrande, Laura; Adams, Ben G.

    2012-01-01

    The September 11, 2001 (9/11), terrorist attacks were unprecedented in their magnitude and aftermath. In the wake of the attacks, researchers reported a wide range of mental and physical health outcomes, with posttraumatic stress disorder (PTSD) the one most commonly studied. In this review, we aim to assess the evidence about PTSD among highly exposed populations in the first 10 years after the 9/11 attacks. We performed a systematic review. Eligible studies included original reports based on the full Diagnostic and Statistical Manual of Mental Disorders (4th ed., rev.; American Psychiatric Association, 2000) criteria of PTSD among highly exposed populations such as those living or working within close proximity to the World Trade Center (WTC) and the Pentagon in New York City and Washington, DC, respectively, and first responders, including rescue, cleaning, and recovery workers. The large body of research conducted after the 9/11 attacks in the past decade suggests that the burden of PTSD among persons with high exposure to 9/11 was substantial. PTSD that was 9/11-related was associated with a wide range of correlates, including sociodemographic and background factors, event exposure characteristics, loss of life of significant others, and social support factors. Few studies used longitudinal study design or clinical assessments, and no studies reported findings beyond six years post-9/11, thus hindering documentation of the long-term course of confirmed PTSD. Future directions for research are discussed. PMID:21823772

  11. Abnormal Functional Connectivity Density in Post-traumatic Stress Disorder.

    PubMed

    Zhang, Youxue; Xie, Bing; Chen, Heng; Li, Meiling; Liu, Feng; Chen, Huafu

    2016-05-01

    Post-traumatic stress disorder (PTSD) is a psychiatric disorder that occurs in individuals who have experienced life-threatening mental traumas. Previous neuroimaging studies have indicated that the pathology of PTSD may be associated with the abnormal functional integration among brain regions. In the current study, we used functional connectivity density (FCD) mapping, a novel voxel-wise data-driven approach based on graph theory, to explore aberrant FC through the resting-state functional magnetic resonance imaging of the PTSD. We calculated both short- and long-range FCD in PTSD patients and healthy controls (HCs). Compared with HCs, PTSD patients showed significantly increased long-range FCD in the left dorsolateral prefrontal cortex (DLPFC), but no abnormal short-range FCD was found in PTSD. Furthermore, seed-based FC analysis of the left DLPFC showed increased connectivity in the left superior parietal lobe and visual cortex of PTSD patients. The results suggested that PTSD patients experienced a disruption of intrinsic long-range functional connections in the fronto-parietal network and visual cortex, which are associated with attention control and visual information processing.

  12. Posttraumatic Stress Disorder after Vaginal Delivery at Primiparous Women

    PubMed Central

    Milosavljevic, Maja; Lecic Tosevski, Dusica; Soldatovic, Ivan; Vukovic, Olivera; Miljevic, Cedo; Peljto, Amir; Kostic, Milutin; Olff, Miranda

    2016-01-01

    Although severe gynaecological pathology during delivery and negative outcome have been shown to be related with posttraumatic stress disorder (PTSD) little is known about traumatic experiences following regular delivery, at the expected time and with a healthy child. The objective of our study was to determine the prevalence of PTSD during postpartum period after vaginal delivery and its risk factors. The sample included 126 primiparous women. Monthly, for the next three months, the women were assessed for PTSD using the gold standard interview for PTSD, Clinician-Administered PTSD Scale (CAPS). Risk factors were assessed including sociodemographic variables, personal medical history and clinical variables. After the first month, 2.4% women had acute full PTSD and another 9.5% had clinically significant level of PTSD symptoms. Following the second and the third month, partial PTSD was found in 5.9% and 1.3% of the women, respectively, and none of participants had full PTSD. Obstetrical interventions were the only significant risk factor for the development of PTSD. Symptoms of postpartum PTSD are not rare after a traumatic delivery, and associated with specific obstetrical risk factors. Awareness of these risk factors may stimulate interventions to prevent this important and neglected postpartum disorder. PMID:27271544

  13. Low Recognition of Posttraumatic Stress Disorder in Primary Care

    PubMed Central

    Ehlers, Anke; Gene-Cos, Nuri; Perrin, Sean

    2013-01-01

    Posttraumatic stress disorder (PTSD) is a common and disabling disorder that develops as a consequence of traumatic events and is characterised by distressing re-experiencing of parts of the trauma, avoidance of reminders, emotional numbing and hyperarousal. The NICE guidelines for PTSD (2005) recommend trauma-focused psychological therapy as the first-line treatment. A survey of 129 general practitioners in South London investigated the recognition and treatment of PTSD in primary care. The majority of GPs underestimated the prevalence of PTSD. Most PTSD patients seen in GP surgeries currently do not receive or are not referred for NICE recommended psychological treatments. Medications, especially SSRIs, appear to more commonly prescribed than recommended by NICE. Efforts to disseminate information about PTSD and effective treatments to both patients and GPs are needed to increase recognition rates and prompter access to treatment. The Improving Access to Psychological Therapies (IAPT) programme will make the NICE recommended treatments more widely available and will allow self-referral by adults with PTSD to trauma-focused psychological therapy. PMID:23814612

  14. Post-traumatic stress disorder and traumatic brain injury.

    PubMed

    Motzkin, Julian C; Koenigs, Michael R

    2015-01-01

    Disentangling the effects of "organic" neurologic damage and psychological distress after a traumatic brain injury poses a significant challenge to researchers and clinicians. Establishing a link between traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) has been particularly contentious, reflecting difficulties in establishing a unique diagnosis for conditions with overlapping and sometimes contradictory symptom profiles. However, each disorder is linked to a variety of adverse health outcomes, underscoring the need to better understand how neurologic and psychiatric risk factors interact following trauma. Here, we present data showing that individuals with a TBI are more likely to develop PTSD, and that individuals with PTSD are more likely to develop persistent cognitive sequelae related to TBI. Further, we describe neurobiological models of PTSD, highlighting how patterns of neurologic damage typical in TBI may promote or protect against the development of PTSD in brain-injured populations. These data highlight the unique course of PTSD following a TBI and have important diagnostic, prognostic, and treatment implications for individuals with a dual diagnosis.

  15. Motor dysfunction during sleep in posttraumatic stress disorder.

    PubMed

    Ross, R J; Ball, W A; Dinges, D F; Kribbs, N B; Morrison, A R; Silver, S M; Mulvaney, F D

    1994-12-01

    A subjective disturbance of sleep, including the occurrence of repetitive, stereotypical anxiety dreams, is characteristic of posttraumatic stress disorder (PTSD). The phenomenology of the PTSD anxiety dream has seemed most consistent with an underlying rapid eye movement (REM) sleep dysfunction. However, motor behavior reportedly can accompany PTSD dreams, and normal REM sleep typically involves a nearly total paralysis of the body musculature. As a means of understanding this discrepancy, anterior tibialis muscle activity during sleep was studied in a group of Vietnam combat veterans with current PTSD and in an age-matched normal control group. The PTSD subjects had a higher percentage of REM sleep epochs with at least one prolonged twitch burst; they also were more likely to have periodic limb movements in sleep, during nonrapid eye movement sleep. Both these forms of muscle activation also have been observed in REM behavior disorder (RBD), a parasomnia characterized by the actual enactment of dream sequences during REM sleep. The identification of RBD-like signs in PTSD adds to the evidence for a fundamental disturbance of REM sleep phasic mechanisms in PTSD.

  16. Latent Factor Structure of DSM-5 Posttraumatic Stress Disorder

    PubMed Central

    Gentes, Emily; Dennis, Paul A.; Kimbrel, Nathan A.; Kirby, Angela C.; Hair, Lauren P.; Beckham, Jean C.; Calhoun, Patrick S.

    2015-01-01

    The current study examined the latent factor structure of posttraumatic stress disorder (PTSD) based on DSM-5 criteria in a sample of participants (N = 374) recruited for studies on trauma and health. Confirmatory factor analyses (CFA) were used to compare the fit of the previous 3-factor DSM-IV model of PTSD to the 4-factor model specified in DSM-5 as well as to a competing 4-factor “dysphoria” model (Simms, Watson, & Doebbeling, 2002) and a 5-factor (Elhai et al., 2011) model of PTSD. Results indicated that the Elhai 5-factor model (re-experiencing, active avoidance, emotional numbing, dysphoric arousal, anxious arousal) provided the best fit to the data, although substantial support was demonstrated for the DSM-5 4-factor model. Low factor loadings were noted for two of the symptoms in the DSM-5 model (psychogenic amnesia and reckless/self-destructive behavior), which raises questions regarding the adequacy of fit of these symptoms with other core features of the disorder. Overall, the findings from the present research suggest the DSM-5 model of PTSD is a significant improvement over the previous DSM-IV model of PTSD. PMID:26366290

  17. Post-traumatic stress disorder following disasters: a systematic review

    PubMed Central

    Neria, Y.; Nandi, A.; Galea, S.

    2016-01-01

    Background Disasters are traumatic events that may result in a wide range of mental and physical health consequences. Post-traumatic stress disorder (PTSD) is probably the most commonly studied post-disaster psychiatric disorder. This review aimed to systematically assess the evidence about PTSD following exposure to disasters. Method A systematic search was performed. Eligible studies for this review included reports based on the DSM criteria of PTSD symptoms. The time-frame for inclusion of reports in this review is from 1980 (when PTSD was first introduced in DSM-III) and February 2007 when the literature search for this examination was terminated. Results We identified 284 reports of PTSD following disasters published in peer-reviewed journals since 1980. We categorized them according to the following classification: (1) human-made disasters (n=90), (2) technological disasters (n=65), and (3) natural disasters (n=116). Since some studies reported on findings from mixed samples (e.g. survivors of flooding and chemical contamination) we grouped these studies together (n=13). Conclusions The body of research conducted after disasters in the past three decades suggests that the burden of PTSD among persons exposed to disasters is substantial. Post-disaster PTSD is associated with a range of correlates including sociodemographic and background factors, event exposure characteristics, social support factors and personality traits. Relatively few studies have employed longitudinal assessments enabling documentation of the course of PTSD. Methodological limitations and future directions for research in this field are discussed. PMID:17803838

  18. Targeting oxidative stress attenuates malonic acid induced Huntington like behavioral and mitochondrial alterations in rats.

    PubMed

    Kalonia, Harikesh; Kumar, Puneet; Kumar, Anil

    2010-05-25

    Objective of the present study was to explore the possible role of oxidative stress in the malonic acid induced behavioral, biochemical and mitochondrial alterations in rats. In the present study, unilateral single injections of malonic acid at different doses (1.5, 3 and 6 micromol) were made into the ipsilateral striatum in rats. Behavioral parameters were accessed on 1st, 7th and 14th day post malonic acid administration. Oxidative stress parameters and mitochondrial enzyme functions were assessed on day 14 after behavioral observations. Ipsilateral striatal malonic acid (3 and 6 micromol) administration significantly reduced body weight, locomotor activity, motor coordination and caused oxidative damage (lipid peroxidation, nitrite, superoxide dismutase, catalase and glutathione) in the striatum as compared to sham treated animal. Mitochondrial enzyme complexes and MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolinium bromide) activity were significantly inhibited by malonic acid. Vitamin E treatment (50 and 100 mg/kg, p.o.) significantly reversed the various behavioral, biochemical and mitochondrial alterations in malonic acid treated animals. Our findings show that targeting oxidative stress by vitamin E in malonic acid model, results in amelioration of behavioral and mitochondrial alterations are linked to inhibition of oxidative damage. Based upon these finding present study hypothesize that protection exerted by vitamin E on behavioral, mitochondrial markers indicates the possible preservation of the functional status of the striatal neurons by targeting the deleterious actions of oxidative stress.

  19. Posttraumatic stress disorder: The development of effective psychological treatments

    PubMed Central

    Ehlers, Anke; Clark, David M.

    2011-01-01

    Posttraumatic stress disorder (PTSD) has only relatively recently been introduced into the diagnostic classification of mental disorders. Building on advances in the treatment of other anxiety disorders, a range of effective psychological treatments for PTSD has been developed. The most effective of these treatments focus on the patient’s memory for the traumatic event and its meaning. This paper briefly reviews the currently available evidence for these treatments. It then illustrates the process of developing effective psychological treatments by discussing how a combination of phenomenological, experimental and treatment development studies and theoretical considerations was used to develop a trauma-focused cognitive-behavioral treatment, Cognitive Therapy (CT) for PTSD. This treatment program builds on Ehlers and Clark’s (2000) model of PTSD, which specifies two core cognitive abnormalities in PTSD. First, people with chronic PTSD show idiosyncratic personal meanings (appraisals) of the trauma and/or its sequelae that lead to a sense of serious current threat. Second, the nature of the trauma memory explains the occurrence of reexperiencing symptoms. It is further proposed that the idiosyncratic appraisals motivate a series of dysfunctional behaviors (such as safety-seeking behaviors) and cognitive strategies (such as thought suppression and rumination) that are intended to reduce the sense of current threat, but maintain the problem by preventing change in the appraisals and trauma memory, and/or lead to increases in symptoms. CT addresses the cognitive abnormalities and maintaining behaviors in an individualized, but focused, way. Four randomized controlled trials and two dissemination studies showed that CT for PTSD is acceptable and effective. PMID:18752113

  20. Cystic Fibrosis-Related Oxidative Stress and Intestinal Lipid Disorders

    PubMed Central

    Kleme, Marie-Laure

    2015-01-01

    Abstract Significance: Cystic fibrosis (CF) is the most common lethal genetic disorder in the Caucasian people. It is due to the mutation of cystic fibrosis transmembrane conductance regulator (CFTR) gene located on the long arm of the chromosome 7, which encodes for CFTR protein. The latter, an adenosine triphosphate binding cassette, is a transmembrane chloride channel that is also involved in glutathione transport. As glutathione/glutathione disulfide constitutes the most important pool of cellular redox systems, CFTR defects could thus disrupt the intracellular redox balance. Resulting multisystemic diseases are essentially characterized by a chronic respiratory failure, a pancreatic insufficiency, an essential fatty acid deficiency (EFAD), and inadequate levels of antioxidant vitamins. Recent Advances: The pathophysiology of CF is complex; however, several mechanisms are proposed, including oxidative stress (OxS) whose implication is recognized and has been clearly demonstrated in CF airways. Critical Issues: Little is known about OxS intrinsic triggers and its own involvement in intestinal lipid disorders. Despite the regular administration of pancreatic supplements, high-fat high-calorie diets, and antioxidant fat-soluble vitamins, there is a persistence of steatorrhea, EFAD, and harmful OxS. Intriguingly, several trials with elevated doses of antioxidant vitamins have not yielded significant improvements. Future Directions: The main sources and self-maintenance of OxS in CF should be clarified to improve treatment of patients. Therefore, this review will discuss the potential sources and study the mechanisms of OxS in the intestine, known to develop various complications, and its involvement in intestinal lipid disorders in CF patients. Antioxid. Redox Signal. 22, 614–631. PMID:25611180

  1. Abnormality of the corpus callosum in coalmine gas explosion-related posttraumatic stress disorder.

    PubMed

    Zhang, Yang; Li, Huabing; Lang, Xu; Zhuo, Chuanjun; Qin, Wen; Zhang, Quan

    2015-01-01

    Abnormal corpus callosum (CC) has been reported in childhood trauma-related posttraumatic stress disorder (PTSD); however, the nature of white matter (WM) integrity alterations in the CC of young adult-onset PTSD patients is unknown. In this study, 14 victims of a coal mine gas explosion with PTSD and 23 matched coal miners without experiencing the coal mine explosion were enrolled. The differences in fractional anisotropy (FA) within 7 sub-regions of the CC were compared between the two groups. Compared to the controls, PTSD coal miners exhibited significantly reduced FA values in the anterior sub-regions of the CC (P < 0.05, Bonferroni-corrected), which mainly interconnect the bilateral frontal cortices. Our findings indicated that the anterior part of the CC was more severely impaired than the posterior part in young adult-onset PTSD, which suggested the patterns of CC impairment may depend on the developmental stage of the structure when the PTSD occurs.

  2. A pilot DTI analysis in patients with recent onset post-traumatic stress disorder

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

    To explore the alteration in white matter between survivors with recent onset post-traumatic stress disorder (PTSD) and without PTSD, who survived from the same coal mine flood disaster, the diffusion tensor imaging (DTI) sequences were analyzed using DTI studio and statistical parametric mapping (SPM) packages in this paper. From DTI sequence, the fractional anisotropy (FA) value describes the degree of anisotropy of a diffusion process, while the apparent diffusion coefficient (ADC) value reflects the magnitude of water diffusion. The DTI analyses between PTSD and non-PTSD indicate lower FA values in the right caudate nucleus, right middle temporal gyrus, right fusiform gyrus, and right superior temporal gyrus, and higher ADC values in the right superior temporal gyrus and right corpus callosum of the subjects with PTSD. These results are partly in line with our previous volume and cortical thickness analyses, indicating the importance of multi-modality analysis for PTSD.

  3. Dimensional assessment of posttraumatic stress disorder in DSM-5.

    PubMed

    LeBeau, Richard; Mischel, Emily; Resnick, Heidi; Kilpatrick, Dean; Friedman, Matthew; Craske, Michelle

    2014-08-15

    The present paper describes the development of the National Stressful Events Survey for PTSD-Short Scale (NSESSS-PTSD), a new self-report scale for PTSD that is brief (9 items), free of copyright restrictions, and consistent with DSM-5 diagnostic criteria. Study 1 describes the development of the NSESSS-PTSD scale items, which were reduced from a larger pool of items that were administered to a subsample of individuals with probable DSM-5 PTSD diagnoses from a large national sample. The resultant scale included items from each criterion and demonstrated high internal consistency. Study 2 evaluates the psychometric properties of the NSESSS-PTSD in a trauma-exposed non-clinical sample. Strong psychometric properties were observed in the sample, including convergent validity (through comparison to the DSM-IV Posttraumatic Stress Disorder Checklist), internal consistency, and the presence of a single dominant factor. Limitations of the present studies are discussed and specific recommendations for the next steps in the validation process are provided.

  4. [Interpersonal psychotherapy (IPT) for post traumatic stress disorder].

    PubMed

    Robertson, Michael

    2008-01-01

    Amongst the many modifications and applications of Interpersonal Psychotherapy (IPT), its utilisation in the treatment of psychological trauma is amongst the most complex. Psychological trauma is usually defined as Post Traumatic Stress Disorder (PTSD) in the Anglo-American literature. Despite the focus of the scientific literature on PTSD, psychological trauma engenders profound disturbances of mood, affect regulation, self-concept, interpersonal adjustment and a profound existential crisis in the lives of those afflicted. In the light of this, no one psychological therapy is positioned to 'treat'all aspects of psychological traumatic stress. Through its focus upon the individual and his or her experience of their interpersonal world, IPT provides scope for a psychological intervention which, whilst aiming at relief of distress, approaches issues not usually addressed in symptom focussed treatments. In this paper, I will attempt to outline the rationale for the use of IPT in psychological trauma and PTSD and then provide some evidence of its utility in the clinical setting.

  5. Unpaired extinction: Implications for treating post-traumatic stress disorder

    PubMed Central

    Schreurs, Bernard G.; Smith-Bell, Carrie A.; Burhans, Lauren B.

    2010-01-01

    Extinction of fear is important for treating stress-related conditions particularly post traumatic stress disorder (PTSD). Although traditional extinction presents the feared stimulus by itself, there is evidence from both clinical and basic research that repeatedly presenting the feared stimulus by itself does not prevent fear from returning. This renewal or relapse can be “thwarted” by unpaired extinction – presentations of the feared stimulus and the event producing the fear. However, no matter how effective standard unpaired extinction may be in the laboratory, repeated presentation of a traumatic event is untenable. To make an unpaired extinction procedure more clinically relevant, we classically conditioned the rabbit nictitating membrane response using electrical stimulation or air puff as the unconditioned stimulus and then during unpaired extinction reduced both the intensity of the unconditioned stimulus and the days of unpaired stimulus presentations. We found unpaired extinction reduced conditioned and exaggerated unconditioned responding (an animal analog of PTSD called conditioning-specific reflex modification) and could be accomplished with a weak unconditioned stimulus as long as extended presentations were used. Surprisingly, brief presentations of a weak unconditioned stimulus or extended presentations of a strong one made the exaggerated responses stronger. One implication is that brief treatment may not just be ineffectual; it may heighten the symptoms of PTSD. Another implication is that using strong stimuli may also heighten those symptoms. PMID:21074779

  6. Bayesian Analysis of Current and Lifetime Comorbidity Rates of Mood and Anxiety Disorders In Individuals with Posttraumatic Stress Disorder

    PubMed Central

    Gallagher, Matthew W.; Brown, Timothy A.

    2014-01-01

    Although posttraumatic stress disorder (PTSD) is no longer considered an anxiety disorder in DSM-5, previous research has indicated high rates of comorbid anxiety and mood disorders in individuals with PTSD. The goal of the present study was to build upon previous examinations of diagnostic comorbidity by using Bayesian methods of estimating current and lifetime comorbidity rates to determine more precise estimates of the proportion of individuals in a clinical sample with PTSD that also meet criteria for various emotional disorders. Two hundred and fifty three individuals with a current or lifetime diagnosis of PTSD underwent a comprehensive assessment of current and lifetime emotional disorders. Bayesian statistical techniques were then used to calculate credibility intervals for the current and lifetime comorbidity rates of emotional disorders. The Bayesian analyses used informative priors based on previous comorbidity findings. The median number of current emotional disorders was two and the median number of lifetime comorbid emotional disorders was three. Credibility intervals indicated that social phobia and major depressive disorder were the most common current and lifetime comorbid emotional disorders. The proportion of individuals with lifetime comorbidity rates were very high for both any lifetime anxiety disorder (.91, 95% CI .88: .94) and any lifetime depressive disorder (.90, 95% CI .86: .93). Together these results indicate that despite the separation from the anxiety disorders in DSM-5, the vast majority of individuals with PTSD will present with one or more emotional disorders. Implications for the assessment and treatment of PTSD are discussed. PMID:26166944

  7. Prenatal stress is a vulnerability factor for altered morphology and biological activity of microglia cells

    PubMed Central

    Ślusarczyk, Joanna; Trojan, Ewa; Głombik, Katarzyna; Budziszewska, Bogusława; Kubera, Marta; Lasoń, Władysław; Popiołek-Barczyk, Katarzyna; Mika, Joanna; Wędzony, Krzysztof; Basta-Kaim, Agnieszka

    2015-01-01

    Several lines of evidence suggest that the dysregulation of the immune system is an important factor in the development of depression. Microglia are the resident macrophages of the central nervous system and a key player in innate immunity of the brain. We hypothesized that prenatal stress (an animal model of depression) as a priming factor could affect microglial cells and might lead to depressive-like disturbances in adult male rat offspring. We investigated the behavioral changes (sucrose preference test, Porsolt test), the expression of C1q and CD40 mRNA and the level of microglia (Iba1 positive) in 3-month-old control and prenatally stressed male offspring rats. In addition, we characterized the morphological and biochemical parameters of potentially harmful (NO, iNOS, IL-1β, IL-18, IL-6, TNF-α, CCL2, CXCL12, CCR2, CXCR4) and beneficial (insulin-like growth factor-1 (IGF-1), brain derived neurotrophic factor (BDNF)) phenotypes in cultures of microglia obtained from the cortices of 1–2 days old control and prenatally stressed pups. The adult prenatally stressed rats showed behavioral (anhedonic- and depression-like) disturbances, enhanced expression of microglial activation markers and an increased number of Iba1-immunopositive cells in the hippocampus and frontal cortex. The morphology of glia was altered in cultures from prenatally stressed rats, as demonstrated by immunofluorescence microscopy. Moreover, in these cultures, we observed enhanced expression of CD40 and MHC II and release of pro-inflammatory cytokines, including IL-1β, IL-18, TNF-α and IL-6. Prenatal stress significantly up-regulated levels of the chemokines CCL2, CXCL12 and altered expression of their receptors, CCR2 and CXCR4 while IGF-1 production was suppressed in cultures of microglia from prenatally stressed rats. Our results suggest that prenatal stress may lead to excessive microglia activation and contribute to the behavioral changes observed in depression in adulthood. PMID

  8. Attention-Deficit/Hyperactivity Disorder in Adult Patients with Posttraumatic Stress Disorder (PTSD): Is ADHD a Vulnerability Factor?

    ERIC Educational Resources Information Center

    Adler, L. A.; Kunz, M.; Chua, H. C.; Rotrosen, J.; Resnick, S. G.

    2004-01-01

    Objective: There is limited evidence suggesting a link between posttraumatic stress disorder (PTSD) and Attention-Deficit/Hyperactivity Disorder (ADHD). This study examined the association between PTSD and ADHD using retrospective and current clinical evaluations. Method: Twenty-five male veterans with PTSD and 22 male veterans with panic …

  9. Traumatic Memories in Acute Stress Disorder: An Analysis of Narratives before and after Treatment

    ERIC Educational Resources Information Center

    Moulds, Michelle L.; Bryant, Richard A.

    2005-01-01

    The dissociative reactions in acute stress disorder purportedly impede encoding and organization of traumatic memories and consequently impair the individual's ability to retrieve trauma-related details. A qualitative examination was conducted on trauma narratives of individuals with acute stress disorder (N = 15) prior to cognitive behavior…

  10. The Incremental Validity and Clinical Utility of the MMPI-2 Infrequency Posttraumatic Stress Disorder Scale

    ERIC Educational Resources Information Center

    Marshall, Margarita B.; Bagby, R. Michael

    2006-01-01

    The incremental validity and clinical utility of the recently developed Minnesota Multiphasic Personality Inventory-2 (MMPI-2) Infrequency Posttraumatic Stress Disorder Scale (Fptsd) was examined in relation to the family of MMPI-2 F scales in distinguishing feigned post-traumatic stress disorder (PTSD) from disability claimants with PTSD.…

  11. The Effect of Post Traumatic Stress Disorder on Military Leadership: An Historical Perspective

    DTIC Science & Technology

    2011-05-19

    Post Traumatic Stress Disorder and Operations Enduring Freedom and Iraqi Freedom: Progress in the Time of Controversy,” Clinical Psychology Review 29...Posttraumatic Stress Disorder and Operating Enduring Freedom and Iraqi Freedom: Progress in a Time of Controversy.” Clinical Psychology Review 29

  12. Cognitive Processing Therapy for Acute Stress Disorder Resulting from an Anti-Gay Assault

    ERIC Educational Resources Information Center

    Kaysen, Debra; Lostutter, Ty W.; Goines, Marie A.

    2005-01-01

    This case study describes Cognitive Processing Therapy (CPT) with a 30-year-old gay man with symptoms of acute stress disorder (ASD) following a recent homophobic assault. Treatment addressed assault-related posttraumatic stress disorder symptoms and depressive symptoms. Also addressed were low self-esteem, helplessness, and high degrees of…

  13. High Self-Perceived Stress and Poor Coping in Intellectually Able Adults with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Hirvikoski, Tatja; Blomqvist, My

    2015-01-01

    Despite average intellectual capacity, autistic traits may complicate performance in many everyday situations, thus leading to stress. This study focuses on stress in everyday life in intellectually able adults with autism spectrum disorders. In total, 53 adults (25 with autism spectrum disorder and 28 typical adults from the general population)…

  14. Validating the Posttraumatic Stress Disorder Symptom Scale with Persons Who Have Severe Mental Illnesses

    ERIC Educational Resources Information Center

    O'Hare, Thomas; Shen, Ce; Sherrer, Margaret

    2007-01-01

    Objective: Interview data collected from 275 clients with severe mental illnesses are used to test the construct and criterion validity of the Posttraumatic Stress Disorder Symptom Scale (PSS). Method: First, exploratory and confirmatory factor analyses are used to test whether the scale reflects the posttraumatic stress disorder (PTSD) symptom…

  15. Factor Structure of the Acute Stress Disorder Scale in a Sample of Hurricane Katrina Evacuees

    ERIC Educational Resources Information Center

    Edmondson, Donald; Mills, Mary Alice; Park, Crystal L.

    2010-01-01

    Acute stress disorder (ASD) is a poorly understood and controversial diagnosis (A. G. Harvey & R. A. Bryant, 2002). The present study used confirmatory factor analysis (CFA) to test the factor structure of the most widely used self-report measure of ASD, the Acute Stress Disorder Scale (R. A. Bryant, M. L. Moulds, & R. M. Guthrie, 2000),…

  16. Altered consolidation of extinction-like inhibitory learning in genotype-specific dysfunctional coping fostered by chronic stress in mice.

    PubMed

    Campus, P; Maiolati, M; Orsini, C; Cabib, S

    2016-12-15

    Genetic and stress-related factors interact to foster mental disorders, possibly through dysfunctional learning. In a previous study we reported that a temporary experience of reduced food availability increases forced swim (FS)-induced helplessness tested 14days after a first experience in mice of the standard inbred C57BL/6(B6) strain but reduces it in mice of the genetically unrelated DBA/2J (D2) strain. Because persistence of FS-induced helplessness influences adaptive coping with stress challenge and involve learning processes the present study tested whether the behavioral effects of restricted feeding involved altered consolidation of FS-related learning. First, we demonstrated that restricted feeding does not influence behavior expressed on the first FS experience, supporting a specific effect on persistence rather then development of helplessness. Second, we found that FS-induced c-fos expression in the infralimbic cortex (IL) was selectively enhanced in food-restricted (FR) B6 mice and reduced in FR D2 mice, supporting opposite alterations of consolidation processes involving this brain area. Third, we demonstrated that immediate post-FS inactivation of IL prevents 24h retention of acquired helplessness by continuously free-fed mice of both strains, indicating the requirement of a functioning IL for consolidation of FS-related learning in either mouse strain. Finally, in line with the known role of IL in consolidation of extinction memories, we found that restricted feeding selectively facilitated 24h retention of an acquired extinction in B6 mice whereas impairing it in D2 mice. These findings support the conclusion that an experience of reduced food availability strain-specifically affects persistence of newly acquired passive coping strategies by altering consolidation of extinction-like inhibitory learning.

  17. Methionine Metabolism Alters Oxidative Stress Resistance via the Pentose Phosphate Pathway.

    PubMed

    Campbell, Kate; Vowinckel, Jakob; Keller, Markus A; Ralser, Markus

    2016-04-01

    Nutrient uptake and metabolism have a significant impact on the way cells respond to stress. The amino acid methionine is, in particular, a key player in the oxidative stress response, and acting as a reactive oxygen species scavenger, methionine is implicated in caloric restriction phenotypes and aging. We here provide evidence that some effects of methionine in stress situations are indirect and caused by altered activity of the nicotinamide adenine dinucleotide phosphate (NADPH) producing oxidative part of the pentose phosphate pathway (PPP). In Saccharomyces cerevisiae, both methionine prototrophic (MET15) and auxotrophic (met15Δ) cells supplemented with methionine showed an increase in PPP metabolite concentrations downstream of the NADPH producing enzyme, 6-phosphogluconate dehydrogenase. Proteomics revealed this enzyme to also increase in expression compared to methionine self-synthesizing cells. Oxidant tolerance was increased in cells preincubated with methionine; however, this effect was abolished when flux through the oxidative PPP was prevented by deletion of its rate limiting enzyme, ZWF1. Stress resistance phenotypes that follow methionine supplementation hence involve the oxidative PPP. Effects of methionine on oxidative metabolism, stress signaling, and aging have thus to be seen in the context of an altered activity of this NADP reducing pathway.

  18. Methionine Metabolism Alters Oxidative Stress Resistance via the Pentose Phosphate Pathway

    PubMed Central

    Campbell, Kate; Vowinckel, Jakob; Keller, Markus A.

    2016-01-01

    Abstract Nutrient uptake and metabolism have a significant impact on the way cells respond to stress. The amino acid methionine is, in particular, a key player in the oxidative stress response, and acting as a reactive oxygen species scavenger, methionine is implicated in caloric restriction phenotypes and aging. We here provide evidence that some effects of methionine in stress situations are indirect and caused by altered activity of the nicotinamide adenine dinucleotide phosphate (NADPH) producing oxidative part of the pentose phosphate pathway (PPP). In Saccharomyces cerevisiae, both methionine prototrophic (MET15) and auxotrophic (met15Δ) cells supplemented with methionine showed an increase in PPP metabolite concentrations downstream of the NADPH producing enzyme, 6-phosphogluconate dehydrogenase. Proteomics revealed this enzyme to also increase in expression compared to methionine self-synthesizing cells. Oxidant tolerance was increased in cells preincubated with methionine; however, this effect was abolished when flux through the oxidative PPP was prevented by deletion of its rate limiting enzyme, ZWF1. Stress resistance phenotypes that follow methionine supplementation hence involve the oxidative PPP. Effects of methionine on oxidative metabolism, stress signaling, and aging have thus to be seen in the context of an altered activity of this NADP reducing pathway. Antioxid. Redox Signal. 24, 543–547. PMID:26596469

  19. Recent Updates on the Dynamic Association Between Oxidative Stress and Neurodegenerative Disorders.

    PubMed

    Khan, Taqi A; Hassan, Iftekhar; Ahmad, Ausaf; Perveen, Asma; Aman, Shazia; Quddusi, Saima; Alhazza, Ibrahim M; Ashraf, Ghulam M; Aliev, Gjumrakch

    2016-01-01

    Free radicals are generated as byproduct of our body metabolism, and their adverse effect on normal functioning of our body is prevented by body's own antioxidant machinery. Any perturbation in the defense mechanism of antioxidants inside body, its abnormal production or its induction from environment to our body lead to serious threats and is responsible for the development of various neurodegenerative disorders (NDDs). Perturbed antioxidants result in sensory and functional impairments in neuronal cells, which in turn cause NDDs. Free radical attack on neuronal cells plays a catastrophic role in NDDs. Impaired metabolism and generation of excessive reactive oxygen species also lead to a range of NDDs. Free radical induced toxicity is responsible for DNA injury, protein degradation, damage to tissue inflammation and cell death. Besides various genetic and environmental factors, free radical induced oxidative stress is also a major cause of NDDs. Application of upstream and downstream antioxidant therapy to counter oxidative stress can be an effective option in alteration of any neuronal impairment besides free radical scavenging. In the present manuscript, we have presented a comprehensive update on the symptoms, causes and cures of NDDs in relation with their dynamic association with oxidative stress.

  20. Post-traumatic stress disorder in different types of stress (clinical features and treatment).

    PubMed

    Rumyantseva, G M; Stepanov, A L

    2008-01-01

    Two types of stress situation were compared: involvement in combat actions and working in the post-Chernobyl atomic energy station clean-up. A total of 30 subjects involved in combat actions (combatants) and 33 clean-up workers were observed for 5-6 years and 15-17 years after involvement in stress situations. Mean ages in the two groups were 27.0 +/- 2.8 and 43.7 +/- 4.5 years respectively. Clinical features were analyzed in terms of the major criteria of post-traumatic stress disorder (PTSD) - "immersion" in the experience, "avoidance," "hyperexcitability," and "social functioning." There were both common features in the two groups of subjects as well as individual characteristics dependent on the nature of the stress. Patients were treated with Coaxil at a dose of 37.5 mg/day for four weeks. In both groups of patients, Coaxil had the most favorable effects on immersion and hyperexcitability, which improved social adaptation. The "avoidance" symptom was more resistant. These studies lead to the conclusion that Coaxil is an effective agent for the treatment of different types of PTSD.

  1. Brain white matter microstructure alterations in adolescent rhesus monkeys exposed to early life stress: associations with high cortisol during infancy

    PubMed Central

    2013-01-01

    Background Early adverse experiences, especially those involving disruption of the mother-infant relationship, are detrimental for proper socioemotional development in primates. Humans with histories of childhood maltreatment are at high risk for developing psychopathologies including depression, anxiety, substance abuse, and behavioral disorders. However, the underlying neurodevelopmental alterations are not well understood. Here we used a nonhuman primate animal model of infant maltreatment to study the long-term effects of this early life stress on brain white matter integrity during adolescence, its behavioral correlates, and the relationship with early levels of stress hormones. Methods Diffusion tensor imaging and tract based spatial statistics were used to investigate white matter integrity in 9 maltreated and 10 control animals during adolescence. Basal plasma cortisol levels collected at one month of age (when abuse rates were highest) were correlated with white matter integrity in regions with group differences. Total aggression was also measured and correlated with white matter integrity. Results We found significant reductions in white matter structural integrity (measured as fractional anisotropy) in the corpus callosum, occipital white matter, external medullary lamina, as well as in the brainstem of adolescent rhesus monkeys that experienced maternal infant maltreatment. In most regions showing fractional anisotropy reductions, opposite effects were detected in radial diffusivity, without changes in axial diffusivity, suggesting that the alterations in tract integrity likely involve reduced myelin. Moreover, in most regions showing reduced white matter integrity, this was associated with elevated plasma cortisol levels early in life, which was significantly higher in maltreated than in control infants. Reduced fractional anisotropy in occipital white matter was also associated with increased social aggression. Conclusions These findings highlight the

  2. Neurobiology of comorbid post-traumatic stress disorder and alcohol-use disorder.

    PubMed

    Gilpin, N W; Weiner, J L

    2017-01-01

    Post-traumatic stress disorder (PTSD) and alcohol-use disorder (AUD) are highly comorbid in humans. Although we have some understanding of the structural and functional brain changes that define each of these disorders, and how those changes contribute to the behavioral symptoms that define them, little is known about the neurobiology of comorbid PTSD and AUD, which may be due in part to a scarcity of adequate animal models for examining this research question. The goal of this review is to summarize the current state-of-the-science on comorbid PTSD and AUD. We summarize epidemiological data documenting the prevalence of this comorbidity, review what is known about the potential neurobiological basis for the frequent co-occurrence of PTSD and AUD and discuss successes and failures of past and current treatment strategies. We also review animal models that aim to examine comorbid PTSD and AUD, highlighting where the models parallel the human condition, and we discuss the strengths and weaknesses of each model. We conclude by discussing key gaps in our knowledge and strategies for addressing them: in particular, we (1) highlight the need for better animal models of the comorbid condition and better clinical trial design, (2) emphasize the need for examination of subpopulation effects and individual differences and (3) urge cross-talk between basic and clinical researchers that is reflected in collaborative work with forward and reverse translational impact.

  3. Acute stress disorder in hospitalised victims of 26/11-terror attack on Mumbai, India.

    PubMed

    Balasinorwala, Vanshree Patil; Shah, Nilesh

    2010-11-01

    The 26/11 terror attacks on Mumbai have been internationally denounced. Acute stress disorder is common in victims of terror. To find out the prevalence and to correlate acute stress disorder, 70 hospitalised victims of terror were assessed for presence of the same using DSM-IV TR criteria. Demographic data and clinical variables were also collected. Acute stress disorder was found in 30% patients. On demographic profile and severity of injury, there were some interesting observations and differences between the victims who developed acute stress disorder and those who did not; though none of the differences reached the level of statistical significance. This study documents the occurrence of acute stress disorder in the victims of 26/11 terror attack.

  4. Evaluation of Oxidative Stress in Bipolar Disorder in terms of Total Oxidant Status, Total Antioxidant Status, and Oxidative Stress Index

    PubMed Central

    CİNGİ YİRÜN, Merve; ÜNAL, Kübranur; ALTUNSOY ŞEN, Neslihan; YİRÜN, Onur; AYDEMİR, Çiğdem; GÖKA, Erol

    2016-01-01

    Introduction Bipolar disorder is one of the most debilitating psychiatric disorders characterized by disruptive episodes of mania/hypomania and depression. Considering the complex role of biological and environmental factors in the etiology of affective disorders, recent studies have focused on oxidative stress, which may damage nerve cell components and take part in pathophysiology. The aim of the present study was to contribute to the data about oxidative stress in bipolar disorder by detecting the total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) levels of manic episode (ME) and euthymic (EU) patients and by comparing these results with those of healthy controls (HCs). Methods The study population consisted of 28 EU outpatients meeting the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for bipolar disorder I and 23 inpatients who were currently hospitalized in a psychiatry ward with the diagnosis of the bipolar disorder ME according to the DSM-5 criteria. Forty-three healthy subjects were included in the study as the control group (HC). Serum TAS, TOS, and OSI levels of all the participants were determined. Results Statistical analysis of serum TAS, TOS, and OSI levels did not show any significant differences between the ME patients, EU patients, and HCs. Comparison between the bipolar disorder patients (ME+EU) and HC also did not reveal any statistically significant difference between these two groups in terms of serum TAS, TOS, and OSI levels. Conclusion To date, studies on oxidative stress in bipolar disorder have led to controversial results. In the present study, no statistically significant difference was detected between the oxidative parameters of bipolar disorder patients and HCs. In order to comprehensively evaluate oxidative stress in bipolar disorder, further studies are needed. PMID:28373794

  5. Hippocampal Transcriptomic and Proteomic Alterations in the BTBR Mouse Model of Autism Spectrum Disorder

    PubMed Central

    Daimon, Caitlin M.; Jasien, Joan M.; Wood, William H.; Zhang, Yongqing; Becker, Kevin G.; Silverman, Jill L.; Crawley, Jacqueline N.; Martin, Bronwen; Maudsley, Stuart

    2015-01-01

    Autism spectrum disorders (ASD) are complex heterogeneous neurodevelopmental disorders of an unclear etiology, and no cure currently exists. Prior studies have demonstrated that the black and tan, brachyury (BTBR) T+ Itpr3tf/J mouse strain displays a behavioral phenotype with ASD-like features. BTBR T+ Itpr3tf/J mice (referred to simply as BTBR) display deficits in social functioning, lack of communication ability, and engagement in stereotyped behavior. Despite extensive behavioral phenotypic characterization, little is known about the genes and proteins responsible for the presentation of the ASD-like phenotype in the BTBR mouse model. In this study, we employed bioinformatics techniques to gain a wide-scale understanding of the transcriptomic and proteomic changes associated with the ASD-like phenotype in BTBR mice. We found a number of genes and proteins to be significantly altered in BTBR mice compared to C57BL/6J (B6) control mice controls such as BDNF, Shank3, and ERK1, which are highly relevant to prior investigations of ASD. Furthermore, we identified distinct functional pathways altered in BTBR mice compared to B6 controls that have been previously shown to be altered in both mouse models of ASD, some human clinical populations, and have been suggested as a possible etiological mechanism of ASD, including “axon guidance” and “regulation of actin cytoskeleton.” In addition, our wide-scale bioinformatics approach also discovered several previously unidentified genes and proteins associated with the ASD phenotype in BTBR mice, such as Caskin1, suggesting that bioinformatics could be an avenue by which novel therapeutic targets for ASD are uncovered. As a result, we believe that informed use of synergistic bioinformatics applications represents an invaluable tool for elucidating the etiology of complex disorders like ASD. PMID:26635614

  6. Hippocampal Transcriptomic and Proteomic Alterations in the BTBR Mouse Model of Autism Spectrum Disorder.

    PubMed

    Daimon, Caitlin M; Jasien, Joan M; Wood, William H; Zhang, Yongqing; Becker, Kevin G; Silverman, Jill L; Crawley, Jacqueline N; Martin, Bronwen; Maudsley, Stuart

    2015-01-01

    Autism spectrum disorders (ASD) are complex heterogeneous neurodevelopmental disorders of an unclear etiology, and no cure currently exists. Prior studies have demonstrated that the black and tan, brachyury (BTBR) T+ Itpr3tf/J mouse strain displays a behavioral phenotype with ASD-like features. BTBR T+ Itpr3tf/J mice (referred to simply as BTBR) display deficits in social functioning, lack of communication ability, and engagement in stereotyped behavior. Despite extensive behavioral phenotypic characterization, little is known about the genes and proteins responsible for the presentation of the ASD-like phenotype in the BTBR mouse model. In this study, we employed bioinformatics techniques to gain a wide-scale understanding of the transcriptomic and proteomic changes associated with the ASD-like phenotype in BTBR mice. We found a number of genes and proteins to be significantly altered in BTBR mice compared to C57BL/6J (B6) control mice controls such as BDNF, Shank3, and ERK1, which are highly relevant to prior investigations of ASD. Furthermore, we identified distinct functional pathways altered in BTBR mice compared to B6 controls that have been previously shown to be altered in both mouse models of ASD, some human clinical populations, and have been suggested as a possible etiological mechanism of ASD, including "axon guidance" and "regulation of actin cytoskeleton." In addition, our wide-scale bioinformatics approach also discovered several previously unidentified genes and proteins associated with the ASD phenotype in BTBR mice, such as Caskin1, suggesting that bioinformatics could be an avenue by which novel therapeutic targets for ASD are uncovered. As a result, we believe that informed use of synergistic bioinformatics applications represents an invaluable tool for elucidating the etiology of complex disorders like ASD.

  7. Prenatal stress alters microglial development and distribution in postnatal rat brain.

    PubMed

    Gómez-González, Beatriz; Escobar, Alfonso

    2010-03-01

    Stress affects microglial function and viability during adulthood and early postnatal life; however, it is unknown whether stress to the pregnant dam might alter offspring microglia. The effects of prenatal stress on microglial development and distribution in the postnatal brain were studied using Wistar rats. Prenatal stress consisting of 20 min of forced swimming occurred on embryonic days 10-20. On postnatal days 1 and 10, stressed and control pups were killed. Microglia were identified using Griffonia simplicifolia lectin and quantified in the whole encephalon. In addition, plasma corticosterone was measured in dams at embryonic day 20, and in pups on postnatal days 1 and 10. At postnatal day 1, there was an increase in number of ramified microglia in the parietal, entorhinal and frontal cortices, septum, basal ganglia, thalamus, medulla oblongata and internal capsule in the stressed pups as compared to controls, but also there was a reduction of amoeboid microglia and the total number of microglia in the corpus callosum. By postnatal day 10, there were no differences in the morphologic type or the distribution of microglia between the prenatal stress and control groups, except in the corpus callosum; where prenatal stress decreased the number of ramified microglia. The stress procedure was effective in producing plasma rise in corticosterone levels of pregnant rats at embryonic day 20 when compared to same age controls. Prenatal stress reduced the number of immature microglia and promoted an accelerated microglial differentiation into a ramified form. These findings may be related to an increase in plasma corticosterone in the pregnant dam.

  8. Trauma exposure relates to heightened stress, altered amygdala morphology and deficient extinction learning: Implications for psychopathology.

    PubMed

    Cacciaglia, Raffaele; Nees, Frauke; Grimm, Oliver; Ridder, Stephanie; Pohlack, Sebastian T; Diener, Slawomira J; Liebscher, Claudia; Flor, Herta

    2017-02-01

    Stress exposure causes a structural reorganization in neurons of the amygdala. In particular, animal models have repeatedly shown that both acute and chronic stress induce neuronal hypertrophy and volumetric increase in the lateral and basolateral nuclei of amygdala. These effects are visible on the behavioral level, where stress enhances anxiety behaviors and provokes greater fear learning. We assessed stress and anxiety levels in a group of 18 healthy human trauma-exposed individuals (TR group) compared to 18 non-exposed matched controls (HC group), and related these measurements to amygdala volume. Traumas included unexpected adverse experiences such as vehicle accidents or sudden loss of a loved one. As a measure of aversive learning, we implemented a cued fear conditioning paradigm. Additionally, to provide a biological marker of chronic stress, we measured the sensitivity of the hypothalamus-pituitary-adrenal (HPA) axis using a dexamethasone suppression test. Compared to the HC, the TR group showed significantly higher levels of chronic stress, current stress and trait anxiety, as well as increased volume of the left amygdala. Specifically, we observed a focal enlargement in its lateral portion, in line with previous animal data. Compared to HC, the TR group also showed enhanced late acquisition of conditioned fear and deficient extinction learning, as well as salivary cortisol hypo-suppression to dexamethasone. Left amygdala volumes positively correlated with suppressed morning salivary cortisol. Our results indicate differences in trauma-exposed individuals which resemble those previously reported in animals exposed to stress and in patients with post-traumatic stress disorder and depression. These data provide new insights into the mechanisms through which traumatic stress might prompt vulnerability for psychopathology.

  9. Are flatter diurnal cortisol rhythms associated with major depression and anxiety disorders in late adolescence? The role of life stress and daily negative emotion.

    PubMed

    Doane, Leah D; Mineka, Susan; Zinbarg, Richard E; Craske, Michelle; Griffith, James W; Adam, Emma K

    2013-08-01

    Alterations in hypothalamic-pituitary-adrenal (HPA) axis functioning have been associated with major depression disorder (MDD) and some anxiety disorders. Few researchers have tested the possibility that high levels of recent life stress or elevations in negative emotion may partially account for the HPA axis alterations observed in these disorders. In a sample of 300 adolescents from the Youth Emotion Project, we examined associations between MDD and anxiety disorders, dimensional measures of internalizing symptomatology, life stress, mood on the days of cortisol testing, and HPA axis functioning. Adolescents with a past MDD episode and those with a recent MDD episode comorbid with an anxiety disorder had flatter diurnal cortisol slopes than adolescents without a history of internalizing disorders. Higher reports of general distress, a dimension of internalizing symptomatology, were also associated with flatter slopes. Negative emotion, specifically sadness and loneliness, was associated with flatter slopes and partially accounted for the associations between comorbid MDD and anxiety disorders and cortisol. The associations between past MDD and cortisol slopes were not accounted for by negative emotion, dimensional variation in internalizing symptomatology, or levels of life stress, indicating that flatter cortisol slopes may also be a "scar" marker of past experiences of MDD.

  10. Post-Traumatic Stress Disorder Predicts Future Weight Change in the Millennium Cohort Study

    DTIC Science & Technology

    2015-04-01

    dis order, or other anxiety disorders (using standardized scoring Patient Health Questionnaire [PHQ] algorithms); (24 26) or (3) reported tak ing...medication for anxiety , stress, or depression were categorized as having a prior mental disorder . Self report of ever being diagnosed by a medical...prospective study of posttraumatic stress disorder symptoms and weight status in women . JAMA psychiatry 2014;71:44-51. 15. Perkonigg A, Owashi T, Stein MB et

  11. Economic Analysis of Post-Traumatic Stress Disorder (PTSD) in the Global War on Terrorism (GWOT)

    DTIC Science & Technology

    2008-12-01

    POST-TRAUMATIC STRESS DISORDER (PTSD) IN THE GLOBAL WAR ON TERRORISM (GWOT) by Boon Wah, Kwan Lai Yee Irene, Tan December 2008 Thesis...REPORT DATE December 2008 3. REPORT TYPE AND DATES COVERED Master’s Thesis 4. TITLE AND SUBTITLE Economic Analysis of Post-traumatic Stress ...This thesis addresses the trend analysis of Post-traumatic Stress Disorder (PTSD) prevalence across the different branches of armed services in the

  12. Post-Traumatic Stress Disorder and the Casual Link to Crime: A Looming National Tragedy

    DTIC Science & Technology

    2008-04-01

    IEDs), suicide bombers and indirect fire all being special stressors, an y several levels of combat related stress that an individual may...Post-traumatic Stress Disorder and the Casual Link to Crime: A Looming National Tragedy A Monograph by MAJ David L. Daniel United States Army...Post-traumatic Stress Disorder and the Casual Link to Crime: A Looming National Tragedy 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6

  13. Cortisol Response to Stress in Adults with Attention Deficit Hyperactivity Disorder

    PubMed Central

    Palomar, Gloria; Ferrer, Roser; Real, Alberto; Nogueira, Mariana; Corrales, Montserrat; Casas, Miguel; Ramos-Quiroga, Josep Antoni

    2015-01-01

    Background: Differences in the cortisol response have been reported between children exhibiting the inattentive and hyperactive/impulsive subtypes of attention deficit hyperactivity disorder. However, there is no such information about adults. The aim of the present study was to determine the possible differences between the combined and inattentive subtypes in the cortisol response to stress. Methods: Ninety-six adults with attention deficit hyperactivity disorder, 38 inattentive and 58 combined, without any medical or psychiatric comorbidities and 25 healthy controls were included. The Trier Social Stress Test was used to assess physiological stress responses. Clinical data and subjective stress levels, including the Perceived Stress Scale, were also recorded. Results: No significant differences in the cortisol response to the Trier Social Stress Test were found between patients and controls. However, albeit there were no basal differences, lower cortisol levels at 15 (P=.015), 30 (P=.015), and 45 minutes (P=.045) were observed in the combined compared with the inattentive subtype after the stress induction; these differences disappeared 60 minutes after the stress. In contrast, the subjective stress responses showed significant differences between attention deficit hyperactivity disorder patients and controls (P<.001), but no differences were seen between attention deficit hyperactivity disorder subtypes. In turn, subjective stress measures, such as the Perceived Stress Scale, positively correlated with the whole cortisol stress response (P<.027). Conclusions: Both the combined and inattentive attention deficit hyperactivity disorder adults exhibited a normal cortisol response to stress when challenged. Nevertheless, the inattentive patients displayed a higher level of cortisol after stress compared with the combined patients. Despite the differences in the cortisol response, adults with attention deficit hyperactivity disorder reported high levels of subjective

  14. Smoking and Posttraumatic Stress Disorder Symptomatology in Orofacial Pain.

    PubMed

    Weber, T; Boggero, I A; Carlson, C R; Bertoli, E; Okeson, J P; de Leeuw, R

    2016-09-01

    To explore the impact of interactions between smoking and symptoms of posttraumatic stress disorder (PTSD) on pain intensity, psychological distress, and pain-related functioning in patients with orofacial pain, a retrospective review was conducted of data obtained during evaluations of 610 new patients with a temporomandibular disorder who also reported a history of a traumatic event. Pain-related outcomes included measures of pain intensity, psychological distress, and pain-related functioning. Main effects of smoking status and PTSD symptom severity on pain-related outcomes were evaluated with linear regression analyses. Further analyses tested interactions between smoking status and PTSD symptom severity on pain-related outcomes. PTSD symptom severity and smoking predicted worse pain-related outcomes. Interaction analyses between PTSD symptom severity and smoking status revealed that smoking attenuated the impact of PTSD symptom severity on affective distress, although this effect was not found at high levels of PTSD symptom severity. No other significant interactions were found, but the present results identifying smoking as an ineffective coping mechanism and the likely role of inaccurate outcome expectancies support the importance of smoking cessation efforts in patients with orofacial pain. Smoking is a maladaptive mechanism for coping with pain that carries significant health- and pain-related risks while failing to fulfill smokers' expectations of affect regulation, particularly among persons with orofacial pain who also have high levels of PTSD symptom severity. Addressing smoking cessation is a critical component of comprehensive treatment. Further research is needed to develop more effective ways to help patients with pain and/or PTSD to replace smoking with more effective coping strategies.

  15. Acacetin promotes healthy aging by altering stress response in Caenorhabditis elegans.

    PubMed

    Asthana, Jyotsna; Mishra, B N; Pandey, Rakesh

    2016-08-01

    The progression in lifespan has been associated with elevated intracellular reactive oxygen species (ROS) and oxidative stress level which contributes to development of age related disorders. The discovery of lifespan modulating phytomolecules may promote development of natural therapies against age related afflictions. Acacetin (5,7-dihydroxy-4-methoxyflavone), is a naturally occurring flavonoid known to possess therapeutic properties. To this end, the present study evaluates effect of acacetin (AC) on lifespan, stress and neurotoxicity for the first time by using well-established free living, multicellular Caenorhabditis elegans model system. The 25 μM dose of AC significantly prolonged the mean lifespan of worms by 27.31% in comparison to untreated control and other tested doses of AC. Additionally, AC enhanced stress resistance against oxidative and thermal stress in worms. Furthermore, AC attenuated age related intracellular ROS level, aggregation of age pigment lipofuscin and increased the mean survival in stress hypersensitive mev-1 mutant by 40.5%. AC supplementation also reduced the alpha synuclein aggregation in transgenic worm model of Parkinson's disease. The enhanced stress resistance, lifespan and alleviation of age related pathology can be attributed to increment in stress modulatory enzymes like superoxide dismutase (SOD) and catalase (CAT) level. Altogether the results suggest AC exposure maintains stress level, health span and extends mean lifespan of C. elegans. The longevity promoting and neuromodulatory effects of AC are mediated by up regulation of the stress response genes sod-3 and gst-4. The present finding gives new insights of natural remedies and their future prospects in developing therapeutic interventions for managing age related diseases.

  16. Posttraumatic Stress Disorder and Risk for Incident Rheumatoid Arthritis

    PubMed Central

    Lee, Yvonne C.; Agnew-Blais, Jessica; Malspeis, Susan; Keyes, Katherine; Costenbader, Karen; Kubzansky, Laura D.; Roberts, Andrea L.; Koenen, Karestan C.; Karlson, Elizabeth W.

    2015-01-01

    Objective To examine the association between symptoms of post-traumatic stress disorder (PTSD) and rheumatoid arthritis (RA) risk in a prospective cohort and to characterize the role of smoking in this relationship. Methods A subset (N = 54,224) of the Nurses’ Health Study II, a prospective cohort of female nurses, completed the Brief Trauma Questionnaire and a screen for PTSD symptoms. Participants were categorized based on trauma exposure and number of PTSD symptoms. Incident RA cases (N = 239) from 1989 to 2011 were identified. Cox proportional hazards models were used to calculate hazard ratios (HRs) and confidence intervals (CIs) between PTSD symptoms and incident RA. To identify the impact of smoking, secondary and subgroup analyses were performed. In all analyses, PTSD and smoking were lagged two years before the development of RA. Results Compared to no history of trauma/PTSD symptoms, the HR for ≥4 PTSD symptoms and incident RA was 1.76 (95% CI 1.16, 2.67) in models adjusted for age, race and socioeconomic status. The risk for RA increased with increasing number of PTSD symptoms (P = 0.01). When smoking was added to the model, the HR for RA remained elevated (HR 1.60; 95% CI 1.05, 2.43). In a subgroup analysis, excluding women who smoked before PTSD onset, results were unchanged (HR 1.68; 95% CI 1.04, 2.70). Conclusion This study suggests that women with high PTSD symptomatology have an elevated risk for RA, independent of smoking, adding to emerging evidence that stress is an important determinant of physical health. PMID:26239524

  17. Impaired Functional Connectivity in the Prefrontal Cortex: A Mechanism for Chronic Stress-Induced Neuropsychiatric Disorders

    PubMed Central

    Negrón-Oyarzo, Ignacio; Aboitiz, Francisco; Fuentealba, Pablo

    2016-01-01

    Chronic stress-related psychiatric diseases, such as major depression, posttraumatic stress disorder, and schizophrenia, are characterized by a maladaptive organization of behavioral responses that strongly affect the well-being of patients. Current evidence suggests that a functional impairment of the prefrontal cortex (PFC) is implicated in the pathophysiology of these diseases. Therefore, chronic stress may impair PFC functions required for the adaptive orchestration of behavioral responses. In the present review, we integrate evidence obtained from cognitive neuroscience with neurophysiological research with animal models, to put forward a hypothesis that addresses stress-induced behavioral dysfunctions observed in stress-related neuropsychiatric disorders. We propose that chronic stress impairs mechanisms involved in neuronal functional connectivity in the PFC that are required for the formation of adaptive representations for the execution of adaptive behavioral responses. These considerations could be particularly relevant for understanding the pathophysiology of chronic stress-related neuropsychiatric disorders. PMID:26904302

  18. Prolonged endoplasmic reticulum stress alters placental morphology and causes low birth weight

    SciTech Connect

    Kawakami, Takashige Yoshimi, Masaki; Kadota, Yoshito; Inoue, Masahisa; Sato, Masao; Suzuki, Shinya

    2014-03-01

    The role of endoplasmic reticulum (ER) stress in pregnancy remains largely unknown. Pregnant mice were subcutaneously administered tunicamycin (Tun), an ER stressor, as a single dose [0, 50, and 100 μg Tun/kg/body weight (BW)] on gestation days (GDs) 8.5, 12.5, and 15.5. A high incidence (75%) of preterm delivery was observed only in the group treated with Tun 100 μg/kg BW at GD 15.5, indicating that pregnant mice during late gestation are more susceptible to ER stress on preterm delivery. We further examined whether prolonged in utero exposure to ER stress affects fetal development. Pregnant mice were subcutaneously administered a dose of 0, 20, 40, and 60 μg Tun/kg from GD 12.5 to 16.5. Tun treatment decreased the placental and fetal weights in a dose-dependent manner. Histological evaluation showed the formation of a cluster of spongiotrophoblast cells in the labyrinth zone of the placenta of Tun-treated mice. The glycogen content of the fetal liver and placenta from Tun-treated mice was lower than that from control mice. Tun treatment decreased mRNA expression of Slc2a1/glucose transporter 1 (GLUT1), which is a major transporter for glucose, but increased placental mRNA levels of Slc2a3/GLUT3. Moreover, maternal exposure to Tun resulted in a decrease in vascular endothelial growth factor receptor-1 (VEGFR-1), VEGFR-2, and placental growth factor. These results suggest that excessive and exogenous ER stress may induce functional abnormalities in the placenta, at least in part, with altered GLUT and vascular-related gene expression, resulting in low infant birth weight. - Highlights: • Maternal exposure to excessive ER stress induced preterm birth and IUGR. • Prolonged excessive ER stress altered the formation of the placental labyrinth. • ER stress decreased GLUT1 mRNA expression in the placenta, but increased GLUT3. • ER stress-induced IUGR causes decreased glycogen and altered glucose transport.

  19. Maternal care interacts with prenatal stress in altering sexual dimorphism in male rats.

    PubMed

    Pérez-Laso, C; Ortega, E; Martín, J L R; Pérez-Izquierdo, M A; Gómez, F; Segovia, S; Del Cerro, M C R

    2013-09-01

    The present study analyzes the interaction between prenatal stress and mother's behavior on brain, hormonal, and behavioral development of male offspring in rats. It extends to males our previous findings, in females, that maternal care can alter behavioral dimorphism that becomes evident in the neonates when they mature. Experiment 1 compares the maternal behavior of foster mothers toward cross-fostered pups versus mothers rearing their own litters. Experiment 2 ascertains the induced "maternal" behavior of the male pups, derived from Experiment 1 when they reached maturity. The most striking effect was that the males non-exposed to the stress as fetuses and raised by stressed foster mothers showed the highest levels of "maternal" behavior of all the groups (i.e., induction of maternal behavior and retrieving behavior), not differing from the control, unstressed, female groups. Furthermore, those males showed significantly fewer olfactory bulb mitral cells than the control males that were non-stressed as fetuses and raised by their own non-stressed mothers. They also presented the lowest levels of plasma testosterone of all the male groups. The present findings provide evidence that prenatal environmental stress can "demasculinize" the behavior, brain anatomy and hormone secretion in the male fetuses expressed when they reach maturity. Moreover, the nature of the maternal care received by neonates can affect the behavior and physiology that they express at maturity.

  20. Relationship between Self-Reported Health and Stress in Mothers of Children with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Reed, Phil; Sejunaite, Karolina; Osborne, Lisa A.

    2016-01-01

    The current study explore the relationship between various forms of experienced stress (general stress and parenting stress) and both health-related quality of life (QoL) and reported physical health symptoms. One hundred and twenty-two mothers of children with autism spectrum disorder responded to an online survey included questionnaires on…

  1. Chronic Stress Induces Structural Alterations in Splenic Lymphoid Tissue That Are Associated with Changes in Corticosterone Levels in Wistar-Kyoto Rats

    PubMed Central

    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. PMID:23533999

  2. Aluminum stress inhibits root growth and alters physiological and metabolic responses in chickpea (Cicer arietinum L.).

    PubMed

    Choudhury, Shuvasish; Sharma, Parul

    2014-12-01

    Chickpea (Cicer arietinum L.) roots were treated with aluminum (Al3+) in calcium chloride (CaCl2) solution (pH 4.7) and growth responses along with physiological and metabolic changes were investigated. Al3+ treatment for 7d resulted in a dose dependent decline of seed germination and inhibition of root growth. A significant (p ≤ 0.05) decline in fresh and dry biomass were observed after 7d of Al3+ stress.The root growth (length) was inhibited after 24 and 48 h of stress imposition. The hydrogen peroxide (H2O2) levels increased significantly (p ≤ 0.05) with respect to control in Al3+ treated roots. The hematoxylin and Evans blue assay indicated significant (p ≤ 0.05) accumulation of Al3+ in the roots and loss of plasma membrane integrity respectively. The time-course evaluation of lipid peroxidation showed increase in malondialdehyde (MDA) after 12, 24 and 48 h of stress imposition. Al3+ treatment did not alter the MDA levels after 2 or 4 h of stress, however, a minor increase was observed after 6 and 10 h of treatment. The proton (1H) nuclear magnetic resonance (NMR) spectrum of the perchloric acid extracts showed variation in the abundance of metabolites and suggested a major metabolic shift in chickpea root during Al3+ stress. The key differences that were observed include changes in energy metabolites. Accumulation of phenolic compounds suggested its possible role in Al3+ exclusion in roots during stress. The results suggested that Al3+ alters growth pattern in chickpea and induces reactive oxygen species (ROS) production that causes physiological and metabolic changes.

  3. Does altering the occlusal vertical dimension produce temporomandibular disorders? A literature review.

    PubMed

    Moreno-Hay, I; Okeson, J P

    2015-11-01

    The purpose of this review was to present a comprehensive review of the scientific evidence available in the literature regarding the effect of altering the occlusal vertical dimens-ion (OVD) on producing temporomandibular disorders. The authors conducted a PubMed search with the following search terms 'temporoman-dibular disorders', 'occlusal vertical dimension', 'stomatognatic system', 'masticatory muscles' and 'skeletal muscle'. Bibliographies of all retrieved articles were consulted for additional publications. Hand-searched publications from 1938 were included. The literature review revealed a lack of well-designed studies. Traditional beliefs have been based on case reports and anecdotal opinions rather than on well-controlled clinical trials. The available evidence is weak and seems to indicate that the stomatognathic system has the ability to adapt rapidly to moderate changes in occlusal vertical dimension (OVD). Nevertheless, it should be taken into consideration that in some patients mild transient symptoms may occur, but they are most often self-limiting and without major consequence. In conclusion, there is no indication that permanent alteration in the OVD will produce long-lasting TMD symptoms. However, additional studies are needed.

  4. Epidemiology of posttraumatic stress disorder: prevalence, correlates and consequences

    PubMed Central

    Atwoli, Lukoye; Stein, Dan J.; Koenen, Karestan C.; McLaughlin, Katie A.

    2015-01-01

    Purpose of review This review discusses recent findings from epidemiological surveys of traumatic events and posttraumatic stress disorder (PTSD) globally, including their prevalence, risk factors, and consequences in the community. Recent findings A number of studies on the epidemiology of PTSD have recently been published from diverse countries, with new methodological innovations introduced. Such work has not only documented the prevalence of PTSD in different settings, but has also shed new light on the PTSD conditional risk associated with specific traumatic events, and on the morbidity and comorbidities associated with these events. Summary Recent community studies show that trauma exposure is higher in lower-income countries compared with high-income countries. PTSD prevalence rates are largely similar across countries, however, with the highest rates being found in postconflict settings. Trauma and PTSD-risk factors are distributed differently in lower-income countries compared with high-income countries, with sociodemographic factors contributing more to this risk in high-income than low-income countries. Apart from PTSD, trauma exposure is also associated with several chronic physical conditions. These findings indicate a high burden of trauma exposure in low-income countries and postconflict settings, where access to trained mental health professionals is typically low. PMID:26001922

  5. Decreased Prolidase Activity in Patients with Posttraumatic Stress Disorder

    PubMed Central

    Bulut, Mahmut; Atli, Abdullah; Kaplan, İbrahim; Kaya, Mehmet Cemal; Bez, Yasin; Özdemir, Pınar Güzel; Sır, Aytekin

    2016-01-01

    Objective Many neurochemical systems have been implicated in the development of Posttraumatic Stress Disorder (PTSD). The prolidase enzyme is a cytosolic exopeptidase that detaches proline or hydroxyproline from the carboxyl terminal position of dipeptides. Prolidase has important biological effects, and to date, its role in the etiology of PTSD has not been studied. In the present study, we aimed to evaluate prolidase activity in patients with PTSD. Methods The study group consisted of patients who were diagnosed with PTSD after the earthquake that occurred in the province of Van in Turkey in 2011 (n=25); the first control group consisted of patients who experienced the earthquake but did not show PTSD symptoms (n=26) and the second control group consisted of patients who have never been exposed to a traumatic event (n=25). Prolidase activities in the patients and the control groups were determined by the ELISA method using commercial kits. Results Prolidase activity in the patient group was significantly lower when compared to the control groups. Prolidase activity was also significantly lower in the traumatized healthy subjects compared to the other healthy group (p<0.01). Conclusion The findings of the present study suggest that the decrease in prolidase activity may have neuroprotective effects in patients with PTSD. PMID:27482243

  6. Management of post traumatic stress disorder after childbirth: a review.

    PubMed

    Lapp, Leann K; Agbokou, Catherine; Peretti, Charles-Siegfried; Ferreri, Florian

    2010-09-01

    Prevalence and risk factors for the development of post traumatic stress disorder (PTSD) after childbirth is well described in the literature. However, its management and treatment has only begun to be investigated. The aim of this article is to describe the studies that examine the effects of interventions on PTSD after childbirth. MedLine, PILOTS, CINAHL and ISI Web of Science databases were systematically searched for randomised controlled trials, pilot studies and case studies using key words related to PTSD, childbirth, treatment and intervention. The reference lists of the retrieved articles were also used to supplement the search. A total of nine studies were retrieved. Seven studies that examined debriefing or counselling were identified; six randomised controlled trials and one pilot study. Also found were one case report describing the effects of cognitive behavioural therapy (CBT) on two women, and one pilot study of eye movement desensitisation and reprocessing (EMDR). Overall, there is limited evidence concerning the management of women with PTSD after childbirth. The results agree with the findings from the non-childbirth related literature: debriefing and counselling are inconclusively effective while CBT and EMDR may improve PTSD status but require investigation in controlled trials before conclusions could be drawn.

  7. Post-traumatic stress disorder in Asian refugees.

    PubMed

    Ton-That, N

    1998-12-01

    This study profiles 127 cases of Vietnamese, Cambodian, Laotian and Chinese refugee outpatients diagnosed with post-traumatic stress disorder (PTSD). Traumatic etiologies included victims of wars such as political refugees, concentration camp prisoners and victims of rape, severe personal losses (property or human lives). These traumata were experienced by our subjects during the period between the end of the Vietnam war in April 1975 and recent times, when they finally arrived in the USA. Clinical symptoms of these subjects reflected many influences of their oriental culture background and are characterized by internalization that needs to be overcome for assessment as well as for therapy. Symptomatic treatment with psychopharmacology and supportive therapy are helpful while cultural approaches have been adopted by many patients to reach the inner self pathology that could be of both mental and organic in nature. These facts need to be taken into consideration in the future description of the PTSD clinical picture. Recommendations are made for future PTSD studies in Vietnam, Cambodia and Laos, and to promote a global movement for prevention of any socio-political situation that may generate PTSD.

  8. Posttraumatic Stress Disorder in Organ Transplant Recipients: A Systematic Review

    PubMed Central

    Davydow, Dimitry S.; Lease, Erika D.; Reyes, Jorge D.

    2015-01-01

    Objective To summarize and critically review the existing literature on the prevalence of posttraumatic stress disorder (PTSD) following organ transplantation, risk factors for post-transplantation PTSD and the relationship of post-transplant PTSD to other clinical outcomes including health-related quality of life (HRQOL) and mortality. Methods We conducted a systematic literature review using PubMed, CINAHL Plus, the Cochrane Library, PsycInfo and a search of the online contents of 18 journals. Results Twenty-three studies were included. Post-transplant, the point prevalence of clinician-ascertained PTSD ranged from 1% to 16% (n = 738), the point prevalence of questionnaire-assessed substantial PTSD symptoms ranged from 0% to 46% (n = 1,024), and the cumulative incidence of clinician-ascertained transplant-specific PTSD ranged from 10% to 17% (n = 482). Consistent predictors of post-transplant PTSD included history of psychiatric illness prior to transplantation and poor social support post-transplantation. Post-transplant PTSD was consistently associated with worse mental HRQOL and potentially associated with worse physical HRQOL. Conclusions PTSD may impact a substantial proportion of organ transplant recipients. Future studies should focus on transplant-specific PTSD, and clarify potential risk factors for, and adverse outcomes related to, post-transplant PTSD. PMID:26073159

  9. Treatment of posttraumatic stress disorder: the impact of paroxetine.

    PubMed

    Davidson, Jonathan R T

    2003-01-01

    The past decade has seen remarkable advances in our ability to treat patients with posttraumatic stress disorder (PTSD). In addition, we are now much more aware of the prevalence of PTSD in civilian populations, and treatment studies now reflect the broad spectrum of patients with PTSD. Findings of studies conducted with the tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), mood stabilizers, and benzodiazepines suggest varying degrees of efficacy, with the MAOIs being particularly efficacious. However, the adverse-effect profiles of these agents, especially the TCAs and the MAOIs, limit their widespread use. The efficacy and tolerability of the selective serotonin reuptake inhibitors (SSRIs), paroxetine, sertraline, and fluoxetine, also have been demonstrated in clinical trials. Paroxetine is especially well studied in this regard, with demonstrated efficacy in men and women, in both short-term and long-term studies, and in combat veterans and civilians. Paroxetine also has been shown to improve quality of life, and to improve sleep disturbances, which can be remarkably disabling, in patients with PTSD. Emerging evidence also suggests that long-term treatment with paroxetine reverses the reductions in hippocampal volume and hypothalamic-pituitary-adrenal axis abnormalities associated with PTSD.

  10. Post-traumatic stress disorder: a right temporal lobe syndrome?

    NASA Astrophysics Data System (ADS)

    Engdahl, B.; Leuthold, A. C.; Tan, H.-R. M.; Lewis, S. M.; Winskowski, A. M.; Dikel, T. N.; Georgopoulos, A. P.

    2010-12-01

    In a recent paper (Georgopoulos et al 2010 J. Neural Eng. 7 016011) we reported on the power of the magnetoencephalography (MEG)-based synchronous neural interactions (SNI) test to differentiate post-traumatic stress disorder (PTSD) subjects from healthy control subjects and to classify them with a high degree of accuracy. Here we show that the main differences in cortical communication circuitry between these two groups lie in the miscommunication of temporal and parietal and/or parieto-occipital right hemispheric areas with other brain areas. This lateralized temporal-posterior pattern of miscommunication was very similar but was attenuated in patients with PTSD in remission. These findings are consistent with observations (Penfield 1958 Proc. Natl Acad. Sci. USA 44 51-66, Penfield and Perot 1963 Brain 86 595-696, Gloor 1990 Brain 113 1673-94, Banceaud et al 1994 Brain 117 71-90, Fried 1997 J. Neuropsychiatry Clin. Neurosci. 9 420-8) that electrical stimulation of the temporal cortex in awake human subjects, mostly in the right hemisphere, can elicit the re-enactment and re-living of past experiences. Based on these facts, we attribute our findings to the re-experiencing component of PTSD and hypothesize that it reflects an involuntarily persistent activation of interacting neural networks involved in experiential consolidation.

  11. Sudden gains in two psychotherapies for posttraumatic stress disorder.

    PubMed

    König, Julia; Karl, Regina; Rosner, Rita; Butollo, Willi

    2014-09-01

    We examined sudden, large, and stable shifts in symptoms from one therapy session to the next in two treatments for posttraumatic stress disorder (PTSD). Shifts in a positive direction (sudden gains) have so far been more frequently analyzed than those in a negative direction (sudden losses). We analyzed data from 102 outpatients suffering from PTSD who received either a cognitive-behavioral or a Gestalt-based intervention. Sudden gains, at 22.5%, were more frequent than sudden losses (3.9% of patients). Participants who had experienced sudden gains had lower PTSD scores at posttreatment, but not at the 6-month follow-up. As sudden losses were so rare, they were not analyzed statistically. Sudden gains accounted for 52% of overall treatment gains or 26% of overall change in a positive direction. Among very successful patients, those with sudden gains were overrepresented, but in absolute terms, there were as many patients without sudden gains in this group. There was no connection between sudden gains and type of intervention or depressive symptoms. Sudden gains and sudden losses occurred in our sample of PTSD patients, but in the light of current results, their clinical importance seems to be limited.

  12. Treatment of sleep disturbances in posttraumatic stress disorder: a review.

    PubMed

    Schoenfeld, Frank B; Deviva, Jason C; Manber, Rachel

    2012-01-01

    Sleep disturbances are among the most commonly reported posttraumatic stress disorder (PTSD) symptoms. It is essential to conduct a careful assessment of the presenting sleep disturbance to select the optimal available treatment. Cognitive-behavioral therapies (CBTs) are at least as effective as pharmacologic treatment in the short-term and more enduring in their beneficial effects. Cognitive-behavioral treatment for insomnia and imagery rehearsal therapy have been developed to specifically treat insomnia and nightmares and offer promise for more effective relief of these very distressing symptoms. Pharmacotherapy continues to be an important treatment choice for PTSD sleep disturbances as an adjunct to CBT, when CBT is ineffective or not available, or when the patient declines CBT. Great need exists for more investigation into the effectiveness of specific pharmacologic agents for PTSD sleep disturbances and the dissemination of the findings to prescribers. The studies of prazosin and the findings of its effectiveness for PTSD sleep disturbance are examples of studies of pharmacologic agents needed in this area. Despite the progress made in developing more specific treatments for sleep disturbances in PTSD, insomnia and nightmares may not fully resolve.

  13. Sex differences in fear conditioning in posttraumatic stress disorder

    PubMed Central

    Inslicht, Sabra S.; Metzler, Thomas J.; Garcia, Natalia M.; Pineles, Suzanne L.; Milad, Mohammed R.; Orr, Scott P.; Marmar, Charles R.; Neylan, Thomas C.

    2013-01-01

    Background Women are twice as likely as men to develop Posttraumatic Stress Disorder (PTSD). Abnormal acquisition of conditioned fear has been suggested as a mechanism for the development of PTSD. While some studies of healthy humans suggest that women are either no different or express less conditioned fear responses during conditioning relative to men, differences in the acquisition of conditioned fear between men and women diagnosed with PTSD has not been examined. Methods Thirty-one participants (18 men; 13 women) with full or subsyndromal PTSD completed a fear conditioning task. Participants were shown computer-generated colored circles that were paired (CS+) or unpaired (CS−) with an aversive electrical stimulus and skin conductance levels were assessed throughout the task. Results Repeated measures ANOVA indicated a significant sex by stimulus interaction during acquisition. Women had greater differential conditioned skin conductance responses (CS + trials compared to CS− trials) than did men, suggesting greater acquisition of conditioned fear in women with PTSD. Conclusions In contrast to studies of healthy individuals, we found enhanced acquisition of conditioned fear in women with PTSD. Greater fear conditioning in women may either be a pre-existing vulnerability trait or an acquired phenomenon that emerges in a sex-dependent manner after the development of PTSD. Characterizing the underlying mechanisms of these differences is needed to clarify sex-related differences in the pathophysiology of PTSD. PMID:23107307

  14. Information Processing Bias in Post-traumatic Stress Disorder

    PubMed Central

    Weber, Darren L

    2008-01-01

    This review considers theory and evidence for abnormal information processing in post-traumatic stress disorder (PTSD). Cognitive studies have indicated sensitivity in PTSD for traumatic information, more so than general emotional information. These findings were supported by neuroimaging studies that identify increased brain activity during traumatic cognition, especially in affective networks (including the amygdala, orbitofrontal and anterior cingulate cortex). In theory, it is proposed that traumatic cognition may interfere with neutral cognition and there is evidence of abnormal neutral stimulus processing in PTSD. Firstly, PTSD patients perform poorly on a variety of neuropsychology tasks that involve attention and memory for neutral information. The evidence from event-related potentials and functional neuroimaging also indicates abnormal results in PTSD during neutral stimulus processing. The research evidence generally provides support for theories of trauma sensitivity and abnormal neutral stimulus processing in PTSD. However, there is only tentative evidence that trauma cognition concurrently interferes with neutral cognition. There is even some evidence that traumatic or novelty arousal processes can increase the capacity for attentive processing, thereby enhancing cognition for neutral stimulus information. Research on this topic has not yet fully explored the mechanisms of interaction between traumatic and neutral content in the cognitive dynamics of PTSD. PMID:19639038

  15. Improvement in cerebral function with treatment of posttraumatic stress disorder.

    PubMed

    Roy, Michael J; Francis, Jennifer; Friedlander, Joshua; Banks-Williams, Lisa; Lande, Raymond G; Taylor, Patricia; Blair, James; McLellan, Jennifer; Law, Wendy; Tarpley, Vanita; Patt, Ivy; Yu, Henry; Mallinger, Alan; Difede, Joann; Rizzo, Albert; Rothbaum, Barbara

    2010-10-01

    Posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) are signature illnesses of the Iraq and Afghanistan wars, but current diagnostic and therapeutic measures for these conditions are suboptimal. In our study, functional magnetic resonance imaging (fMRI) is used to try to differentiate military service members with: PTSD and mTBI, PTSD alone, mTBI alone, and neither PTSD nor mTBI. Those with PTSD are then randomized to virtual reality exposure therapy or imaginal exposure. fMRI is repeated after treatment and along with the Clinician-Administered PTSD Scale (CAPS) and Clinical Global Impression (CGI) scores to compare with baseline. Twenty subjects have completed baseline fMRI scans, including four controls and one mTBI only; of 15 treated for PTSD, eight completed posttreatment scans. Most subjects have been male (93%) and Caucasian (83%), with a mean age of 34. Significant improvements are evident on fMRI scans, and corroborated by CGI scores, but CAPS scores improvements are modest. In conclusion, CGI scores and fMRI scans indicate significant improvement in PTSD in both treatment arms, though CAPS score improvements are less robust.

  16. Coenzyme Q10 ameliorates oxidative stress and prevents mitochondrial alteration in ischemic retinal injury.

    PubMed

    Lee, Dongwook; Kim, Keun-Young; Shim, Myoung Sup; Kim, Sang Yeop; Ellisman, Mark H; Weinreb, Robert N; Ju, Won-Kyu

    2014-04-01

    Coenzyme Q10 (CoQ10) acts by scavenging reactive oxygen species for protecting neuronal cells against oxidative stress in neurodegenerative diseases. We tested whether a diet supplemented with CoQ10 ameliorates oxidative stress and mitochondrial alteration, as well as promotes retinal ganglion cell (RGC) survival in ischemic retina induced by intraocular pressure elevation. A CoQ10 significantly promoted RGC survival at 2 weeks after ischemia. Superoxide dismutase 2 (SOD2) and heme oxygenase-1 (HO-1) expression were significantly increased at 12 h after ischemic injury. In contrast, the CoQ10 significantly prevented the upregulation of SOD2 and HO-1 protein expression in ischemic retina. In addition, the CoQ10 significantly blocked activation of astroglial and microglial cells in ischemic retina. Interestingly, the CoQ10 blocked apoptosis by decreasing caspase-3 protein expression in ischemic retina. Bax and phosphorylated Bad (pBad) protein expression were significantly increased in ischemic retina at 12 h. Interestingly, while CoQ10 significantly decreased Bax protein expression in ischemic retina, CoQ10 showed greater increase of pBad protein expression. Of interest, ischemic injury significantly increased mitochondrial transcription factor A (Tfam) protein expression in the retina at 12 h, however, CoQ10 significantly preserved Tfam protein expression in ischemic retina. Interestingly, there were no differences in mitochondrial DNA content among control- or CoQ10-treated groups. Our findings demonstrate that CoQ10 protects RGCs against oxidative stress by modulating the Bax/Bad-mediated mitochondrial apoptotic pathway as well as prevents mitochondrial alteration by preserving Tfam protein expression in ischemic retina. Our results suggest that CoQ10 may provide neuroprotection against oxidative stress-mediated mitochondrial alterations in ischemic retinal injury.

  17. Impact of traumatic events on posttraumatic stress disorder among Danish survivors of sexual abuse in childhood.

    PubMed

    Elklit, Ask; Christiansen, Dorte M; Palic, Sabina; Karsberg, Sidsel; Eriksen, Sara Bek

    2014-01-01

    Childhood sexual abuse can be extremely traumatic and lead to lifelong symptomatology. The present study examined the impact of several demographic, abuse, and psychosocial variables on posttraumatic stress disorder severity among a consecutive sample of treatment-seeking, adult child sexual abuse survivors (N = 480). The child sexual abuse sample was characterized by severe trauma exposure, insecure attachment, and significant traumatization, with an estimated 77% suffering from posttraumatic stress disorder, more than twice the level of the comparison group. Regression analyses revealed risk factors associated with the development of posttraumatic stress disorder in which the strongest predictors being additional traumas, negative affectivity, and somatization. The findings add to existing research confirming the stressful nature of child sexual abuse and the variables that contribute to the development and severity of posttraumatic stress disorder.

  18. New avenues for treating emotional memory disorders: towards a reconsolidation intervention for posttraumatic stress disorder

    PubMed Central

    Kindt, Merel; van Emmerik, Arnold

    2016-01-01

    The discovery that fear memories may change upon retrieval, a process referred to as memory reconsolidation, opened avenues to develop a revolutionary new treatment for emotional memory disorders. Reconsolidation is a two-phase process in which retrieval of a memory initiates a transient period of memory destabilization, followed by a protein synthesis-dependent restabilization phase. This reconsolidation window offers unique opportunities for amnesic agents to interfere with the process of memory restabilization, thereby weakening or even erasing the emotional expression from specific fear memories. Here we present four uncontrolled case descriptions of patients with symptoms of posttraumatic stress disorder (PTSD) who received a reconsolidation intervention. The intervention basically involves a brief reactivation of the trauma memory aimed to trigger memory destabilization, followed by the intake of one pill of 40 mg propranolol HCl (i.e. a noradrenergic beta-blocker) that should disrupt the process of memory restabilization. We present three cases who showed a steep decline of fear symptoms after only one or two intervention sessions. To illustrate that the translation from basic science to clinical practice is not self-evident, we also present a description of a noneffective intervention in a relatively complex case. Even though the reconsolidation intervention is very promising, the success of the treatment depends on whether the memory reactivation actually triggers memory reconsolidation. Obviously the uncontrolled observations described here warrant further study in placebo-controlled designs. PMID:27536348

  19. Altered activity of the serratus anterior during unilateral arm elevation in patients with cervical disorders.

    PubMed

    Helgadottir, H; Kristjansson, E; Einarsson, E; Karduna, A; Jonsson, H

    2011-12-01

    Altered activity in the axioscapular muscles is considered to be an important feature in patients with neck pain. The activity of the serratus anterior (SA) and trapezius muscles during arm elevation has not been investigated in these patients. The objectives of this study was to investigate whether there is a pattern of altered activity in the SA and trapezius in patients with insidious onset neck pain (IONP) (n=22) and whiplash associated disorders (WAD) (n=27). An asymptomatic group was selected for baseline measurements (n=23). Surface electromyography was used to measure the onset of muscle activation and duration of muscle activity of the SA as well as the upper, middle, and lower trapezius during unilateral arm elevation in the three subject groups. Both arms were tested. With no interaction, the main effect for the onset of muscle activation and duration of muscle activity for serratus anterior was statistically significant among the groups. Post hoc comparison revealed a significantly delayed onset of muscle activation and less duration of muscle activity in the IONP group, and in the WAD group compared to the asymptomatic group. There were no group main effects or interaction effects for upper, middle and lower trapezius. This finding may have implications for scapular stability in these patients because the altered activity in the SA may reflect inconsistent or poorly coordinated muscle activation that may reduce the quality of neuromuscular performance and induce an increased load on the cervical and the thoracic spine.

  20. Mitochondrial damage associated with long-term antiretroviral treatment: associated alteration or causal disorder?

    PubMed

    Vittecoq, Daniel; Jardel, Claude; Barthélémy, Cyrille; Escaut, Lélia; Cheminot, Nathalie; Chapin, Sandrine; Sternberg, Damien; Maisonobe, Thierry; Lombès, Anne

    2002-11-01

    Combination of antiretroviral drugs has dramatically improved the prognosis of human HIV infection but is also associated with many adverse effects, the mitochondrial origin of which is discussed. In this study using extensive diagnostic procedures set up for inherited mitochondrial disorders, we analyzed HIV patients under active antiretroviral therapy who complained of severe adverse symptoms unexplained by HIV. All these patients had been treated for at least 5 years. They all had significant mitochondrial damage as evidenced by the diverse combination of lactate accumulation in blood or cerebrospinal fluid, mitochondrial morphologic alterations in muscle, and biochemical defects in muscle and liver, which designated mitochondrial DNA (mtDNA) as the main target of the toxic mechanisms. Southern blot and/or polymerase chain reaction -based analyses disclosed multiple deletions of the muscle mtDNA and reduction of the muscle and/or liver mtDNA copy number in a majority of the patients. In opposition to muscle and liver, blood mononuclear cells were devoid of significant biochemical or genetic alterations. Whether the mitochondrial toxicity is directly responsible for the patients' adverse symptoms remains disputable, because the investigations were transversal. Its severity argues for its clinical relevance, however. The skewed tissue distribution of mitochondrial alterations indicates potential pitfalls in the needed future prospective studies.

  1. Prospective Analysis of Risk Factors Related to Depression and Post Traumatic Stress Disorder in Deployed United States Navy Personnel

    DTIC Science & Technology

    2011-03-28

    34Prospective Analysis of Risk Factors Related to Depression and Post Traumatic Stress Disorder in Deployed United States Navy Personnel" Name of...Risk Factors Related to Depression and Post Traumatic Stress Disorder in Deployed United States...Dissertation: Prospective Analysis of Risk Factors Related to Depression and Post Traumatic Stress Disorder in Deployed United States Navy Personnel

  2. Imaging genetics in obsessive-compulsive disorder: linking genetic variations to alterations in neuroimaging.

    PubMed

    Grünblatt, Edna; Hauser, Tobias U; Walitza, Susanne

    2014-10-01

    Obsessive-compulsive disorder (OCD) occurs in ∼1-3% of the general population, and its often rather early onset causes major disabilities in the everyday lives of patients. Although the heritability of OCD is between 35 and 65%, many linkage, association, and genome-wide association studies have failed to identify single genes that exhibit high effect sizes. Several neuroimaging studies have revealed structural and functional alterations mainly in cortico-striato-thalamic loops. However, there is also marked heterogeneity across studies. These inconsistencies in genetic and neuroimaging studies may be due to the heterogeneous and complex phenotypes of OCD. Under the consideration that genetic variants may also influence neuroimaging in OCD, researchers have started to combine both domains in the field of imaging genetics. Here, we conducted a systematic search of PubMed and Google Scholar literature for articles that address genetic imaging in OCD and related disorders (published through March 2014). We selected 8 publications that describe the combination of imaging genetics with OCD, and extended it with 43 publications of comorbid psychiatric disorders. The most promising findings of this systematic review point to the involvement of variants in genes involved in the serotonergic (5-HTTLPR, HTR2A), dopaminergic (COMT, DAT), and glutamatergic (SLC1A1, SAPAP) systems. However, the field of imaging genetics must be further explored, best through investigations that combine multimodal imaging techniques with genetic profiling, particularly profiling techniques that employ polygenetic approaches, with much larger sample sizes than have been used up to now.

  3. Alterations in membrane trafficking and pathophysiological implications in lysosomal storage disorders.

    PubMed

    Kuech, Eva-Maria; Brogden, Graham; Naim, Hassan Y

    2016-11-01

    Lysosomal storage disorders are a heterogeneous group of more than 50 distinct inborn metabolic diseases affecting about 1 in 5000 to 7000 live births. The diseases often result from mutations followed by functional deficiencies of enzymes or transporters within the acidic environment of the lysosome, which mediate the degradation of a wide subset of substrates, including glycosphingolipids, glycosaminoglycans, cholesterol, glycogen, oligosaccharides, peptides and glycoproteins, or the export of the respective degradation products from the lysosomes. The progressive accumulation of uncleaved substrates occurs in multiple organs and finally causes a broad spectrum of different pathologies including visceral, neurological, skeletal and hematologic manifestations. Besides deficient lysosomal enzymes and transporters other defects may lead to lysosomal storage disorders, including activator defects, membrane defects or defects in modifier proteins. In this review we concentrate on four different lysosomal storage disorders: Niemann-Pick type C, Fabry disease, Gaucher disease and Pompe disease. While the last three are caused by defective lysosomal hydrolases, Niemann-Pick type C is caused by the inability to export LDL-derived cholesterol out of the lysosome. We want to emphasise potential implications of membrane trafficking defects on the pathology of these diseases, as many mutations interfere with correct lysosomal protein trafficking and alter cellular lipid homeostasis. Current therapeutic strategies are summarised, including substrate reduction therapy as well as pharmacological chaperone therapy which directly aim to improve folding and lysosomal transport of misfolded mutant proteins.

  4. Structural impairments of hippocampus in coal mine gas explosion-related posttraumatic stress disorder.

    PubMed

    Zhang, Quan; Zhuo, Chuanjun; Lang, Xu; Li, Huabing; Qin, Wen; Yu, Chunshui

    2014-01-01

    Investigations on hippocampal and amygdalar volume have revealed inconsistent results in patients with posttraumatic stress disorder (PTSD). Little is known about the structural covariance alterations between the hippocampus and amygdala in PTSD. In this study, we evaluated the alteration in the hippocampal and amygdalar volume and their structural covariance in the coal mine gas explosion related PTSD. High resolution T1-weighted magnetic resonance imaging (MRI) was performed on coal mine gas explosion related PTSD male patients (n = 14) and non-traumatized coalminers without PTSD (n = 25). The voxel-based morphometry (VBM) method was used to test the inter-group differences in hippocampal and amygdalar volume as well as the inter-group differences in structural covariance between the ipsilateral hippocampus and amygdala. PTSD patients exhibited decreased gray matter volume (GMV) in the bilateral hippocampi compared to controls (p<0.05, FDR corrected). GMV covariances between the ipsilateral hippocampus and amygdala were significantly reduced in PTSD patients compared with controls (p<0.05, FDR corrected). The coalminers with gas explosion related PTSD had decreased hippocampal volume and structural covariance with the ipsilateral amygdala, suggesting that the structural impairment of the hippocampus may implicate in the pathophysiology of PTSD.

  5. Anomalous gray matter structural networks in recent onset post-traumatic stress disorder.

    PubMed

    Qi, Shun; Mu, Yun-Feng; Cui, Long-Biao; Zhang, Jian; Guo, Fan; Tan, Qing-Rong; Shi, Mei; Liu, Kang; Xi, Yi-Bin; Zhang, Nan-Yin; Zhang, Xiao-Liang; He, Yong; Yang, Jian; Yin, Hong

    2017-03-14

    Alterations of the topological organization of abnormal regions or network-level structural aberrations are still poorly understood for post-traumatic stress disorder (PTSD). Herein, we investigated brain structural networks in recent-onset PTSD patients, all affected by the coalmine-flood disaster. Cortical networks were studied in recent onset PTSD patients (n = 15) and matched healthy controls (n = 25). Cortical networks were constructed by thresholding correlation matrices of 150 regions and quantified using graph theoretical approaches. Contributions of high-degree nodes, and regional and global network measures, including degree and betweenness, were studied. Compared with healthy controls, PTSD patients showed altered quantitative values in global network properties, characterized by shorter path length and higher clustering. Moreover, PTSD patients exhibited decreased connectivity in the right lingual gyrus, parahippocampal gyrus, left supramarginal gyrus, parahippocampal gyrus, bilateral superior and inferior frontal gyrus, superior frontal gyrus, and posterior cingulate gyrus. Nodal centrality decreased predominantly in the occipital regions (lingual gyrus) and default-mode regions, while increased correlations and centralities were observed in the medial temporal lobe and posterior cingulate cortex. PTSD-related networks exhibited a less efficient organization and regional connectivity. According to these findings, we conclude that regional connections involving fear-processing and re-experiential-processing cortex may play a role in maintaining or adapting to PTSD pathology.

  6. Disrupted resting-state insular subregions functional connectivity in post-traumatic stress disorder

    PubMed Central

    Zhang, Youxue; Xie, Bing; Chen, Heng; Li, Meiling; Guo, Xiaonan; Chen, Huafu

    2016-01-01

    Abstract Post-traumatic stress disorder (PTSD) is suggested to be a structural and functional abnormality in the insula. The insula, which consists of distinct subregions with various patterns of connectivity, displays complex and diverse functions. However, whether these insular subregions have different patterns of connectivity in PTSD remains unclear. Investigating the abnormal functional connectivity of the insular subregions is crucial to reveal its potential effect on diseases specifically PTSD. This study uses a seed-based method to investigate the altered resting-state functional connectivity of insular subregions in PTSD. We found that patients with PTSD showed reduced functional connectivity compared with healthy controls (HCs) between the left ventral anterior insula and the anterior cingulate cortex. The patients with PTSD also exhibited decreased functional connectivity between the right posterior insula and left inferior parietal lobe, and the postcentral gyrus relative to HCs. These results suggest the involvement of altered functional connectivity of insular subregions in the abnormal regulation of emotion and processing of somatosensory information in patients with PTSD. Such impairments in functional connectivity patterns of the insular subregions may advance our understanding of the pathophysiological basis underlying PTSD. PMID:27399097

  7. Disrupted resting-state insular subregions functional connectivity in post-traumatic stress disorder.

    PubMed

    Zhang, Youxue; Xie, Bing; Chen, Heng; Li, Meiling; Guo, Xiaonan; Chen, Huafu

    2016-07-01

    Post-traumatic stress disorder (PTSD) is suggested to be a structural and functional abnormality in the insula. The insula, which consists of distinct subregions with various patterns of connectivity, displays complex and diverse functions. However, whether these insular subregions have different patterns of connectivity in PTSD remains unclear. Investigating the abnormal functional connectivity of the insular subregions is crucial to reveal its potential effect on diseases specifically PTSD. This study uses a seed-based method to investigate the altered resting-state functional connectivity of insular subregions in PTSD. We found that patients with PTSD showed reduced functional connectivity compared with healthy controls (HCs) between the left ventral anterior insula and the anterior cingulate cortex. The patients with PTSD also exhibited decreased functional connectivity between the right posterior insula and left inferior parietal lobe, and the postcentral gyrus relative to HCs. These results suggest the involvement of altered functional connectivity of insular subregions in the abnormal regulation of emotion and processing of somatosensory information in patients with PTSD. Such impairments in functional connectivity patterns of the insular subregions may advance our understanding of the pathophysiological basis underlying PTSD.

  8. Disrupted rapid eye movement sleep predicts poor declarative memory performance in post-traumatic stress disorder.

    PubMed

    Lipinska, Malgorzata; Timol, Ridwana; Kaminer, Debra; Thomas, Kevin G F

    2014-06-01

    Successful memory consolidation during sleep depends on healthy slow-wave and rapid eye movement sleep, and on successful transition across sleep stages. In post-traumatic stress disorder, sleep is disrupted and memory is impaired, but relations between these two variables in the psychiatric condition remain unexplored. We examined whether disrupted sleep, and consequent disrupted memory consolidation, is a mechanism underlying declarative memory deficits in post-traumatic stress disorder. We recruited three matched groups of participants: post-traumatic stress disorder (n = 16); trauma-exposed non-post-traumatic stress disorder (n = 15); and healthy control (n = 14). They completed memory tasks before and after 8 h of sleep. We measured sleep variables using sleep-adapted electroencephalography. Post-traumatic stress disorder-diagnosed participants experienced significantly less sleep efficiency and rapid eye movement sleep percentage, and experienced more awakenings and wake percentage in the second half of the night than did participants in the other two groups. After sleep, post-traumatic stress disorder-diagnosed participants retained significantly less information on a declarative memory task than controls. Rapid eye movement percentage, wake percentage and sleep efficiency correlated with retention of information over the night. Furthermore, lower rapid eye movement percentage predicted poorer retention in post-traumatic stress disorder-diagnosed individuals. Our results suggest that declarative memory consolidation is disrupted during sleep in post-traumatic stress disorder. These data are consistent with theories suggesting that sleep benefits memory consolidation via predictable neurobiological mechanisms, and that rapid eye movement disruption is more than a symptom of post-traumatic stress disorder.

  9. Can pediatric bipolar-I disorder be diagnosed in the context of posttraumatic stress disorder? A familial risk analysis.

    PubMed

    Biederman, Joseph; Wozniak, Janet; Martelon, Mary Kate; Spencer, Thomas J; Woodworth, Yvonne; Joshi, Gagan; Spencer, Andrea; Uchida, Mai; Kotte, Amelia; Faraone, Stephen V

    2013-08-15

    Despite ongoing concerns that traumatized children with severe symptoms of emotional dysregulation may be inappropriately receiving a diagnosis of pediatric bipolar-I (BP-I) disorder, this issue has not been adequately examined in the literature. Because both pediatric BP-I disorder and posttraumatic stress disorder (PTSD) are familial disorders, if children with both BP-I and PTSD were to be truly affected with BP-I disorder, their relatives would be at high risk for BP-I disorder. To this end, we compared patterns of familial aggregation of BP-I disorder in BP-I children with and without PTSD with age and sex matched controls. Participants were 236 youths with BP-I disorder and 136 controls of both sexes along with their siblings. Participants completed a large battery of measures designed to assess psychiatric disorders, psychosocial, educational, and cognitive parameters. Familial risk analysis revealed that relatives of BP-I probands with and without PTSD had similar elevated rates of BP-I disorder that significantly differed from those of relatives of controls. Pediatric BP-I disorder is similarly highly familial in probands with and without PTSD indicating that their co-occurrence is not due to diagnostic error.

  10. Associations between lower order anxiety sensitivity dimensions and DSM-5 posttraumatic stress disorder symptoms.

    PubMed

    Raines, Amanda M; Walton, Jessica L; McManus, Eliza S; Cuccurullo, Lisa-Ann J; Chambliss, Jessica; Uddo, Madeline; Franklin, C Laurel

    2017-03-01

    Anxiety sensitivity (AS), a well-established individual difference variable reflecting a tendency to fear bodily sensations associated with arousal, has been implicated in the development and maintenance of posttraumatic stress disorder (PTSD). Despite these associations, little research has examined the relations between AS subfactors (eg physical, cognitive, and social) and PTSD symptoms and none have examined these associations in the context of DSM-5 (Diagnostic Statistical Manual of Mental Disorders, Fifth Edition) PTSD clusters (ie intrusion, avoidance, negative alterations in cognitions/mood, and arousal). Participants included 50 veterans presenting to an outpatient Veteran Affairs Clinic for psychological services. Upon intake, veterans completed a brief battery of self-report questionnaires to assist with differential diagnosis and treatment planning. Results revealed unique associations between lower order AS dimensions, in particular the cognitive concerns dimension, and all four DSM-5 PTSD symptom clusters. Given the malleable nature of AS cognitive concerns, as well as the growing number of veterans in need of care, future research should determine the extent to which targeting this cognitive risk factor reduces PTSD symptom severity among veterans.

  11. Acute stress disorder, depression, and tobacco use in disaster workers following 9/11.

    PubMed

    Biggs, Quinn M; Fullerton, Carol S; Reeves, James J; Grieger, Thomas A; Reissman, Dori; Ursano, Robert J

    2010-10-01

    Early posttraumatic psychiatric disorders have not been well studied in disaster workers. This study examined the rates of probable acute stress disorder (ASD), probable depression, increased tobacco use, and their associated risk factors in 9/11 World Trade Center disaster workers. Surveys were obtained from 90 disaster workers (e.g., medical personnel, police, firefighters, search and rescue) 2-3 weeks after 9/11. Nearly 15% of disaster workers had probable ASD and 26% had probable depression. Probable ASD and depression were highly related to functional impairment. The risk for ASD was increased for those with 9/11-specific disaster exposures, more pre-9/11 trauma exposures, and the peritraumatic dissociative symptom of altered sense of time. Disaster workers who were younger, non-White, or who had increasing numbers of peritraumatic dissociative symptoms were more likely to have probable depression. More than half of tobacco users increased their tobacco use after 9/11. Additionally, all tobacco users with probable ASD and almost all tobacco users with probable depression increased tobacco use. Rapid mobilization of resources for early screening and intervention and health promotion campaigns aimed at improving adverse health-related behaviors may be helpful for this high-risk group.

  12. Effects of Estradiol on Post-Traumatic Stress Disorder Symptoms

    DTIC Science & Technology

    2010-03-01

    include, exaggerated startle responses, irritability or aggression, social avoidance or inhibition, and memory dysfunction 16. Techniques used thus...inescapable foot shock), (2) aversive signals (a predator, predator odor, or social stress), (3) single prolonged stress (2hr restraint stress, 20 minutes of...responsible for emotional memories and regulation of the stress response (amygdala, hippocampus and prefrontal cortex) 19-21. Acute immobilization

  13. Mice lacking integrin β3 expression exhibit altered response to chronic stress

    PubMed Central

    Varney, Seth; Polston, Keith F.; Jessen, Tammy; Carneiro, Ana M.D.

    2015-01-01

    Recent studies indicate multiple roles for integrin αvβ3 in adult neurons, including response to pharmacological agents such as cocaine and selective serotonin reuptake inhibitors. In this study, we examined the role of the integrin β3 gene (Itgb3) in the response to environmental stimuli by subjecting Itgb3+/+ and Itgb3−/− mice to unpredictable chronic mild stressors. We found that genetic abrogation of integrin β3 expression elicits an exaggerated vulnerability to chronic unpredictable stress in the open field test. In this test, chronic stress elicited significant decreases in stereotypic behavior and horizontal locomotor activity, including increases in anxiety behaviors. Mild chronic stress led to reductions in dopamine turnover in midbrains of Itgb3+/+, but not Itgb3−/− mice, suggesting a disruption of stress-dependent regulation of DA homeostasis. Chronic stress elicited altered synaptic expression of syntaxin and synaptophysin in midbrains of Itgb3−/− mice, when compared to Itgb3+/+. Semi-quantitative Western blot studies revealed that the synaptic expression, but not total tissue expression, of multiple signaling proteins is correlated with integrin αv levels in the midbrain. Moreover, loss of integrin β3 expression modifies this correlation network. Together, these findings demonstrate that Itgb3−/− mice display a pattern of changes indicating disrupted regulation of midbrain synaptic systems involved in conferring resilience to mild stressors. PMID:26634222

  14. Stress-Related Alterations of Visceral Sensation: Animal Models for Irritable Bowel Syndrome Study

    PubMed Central

    Mulak, Agata; Taché, Yvette

    2011-01-01

    Stressors of different psychological, physical or immune origin play a critical role in the pathophysiology of irritable bowel syndrome participating in symptoms onset, clinical presentation as well as treatment outcome. Experimental stress models applying a variety of acute and chronic exteroceptive or interoceptive stressors have been developed to target different periods throughout the lifespan of animals to assess the vulnerability, the trigger and perpetuating factors determining stress influence on visceral sensitivity and interactions within the brain-gut axis. Recent evidence points towards adequate construct and face validity of experimental models developed with respect to animals' age, sex, strain differences and specific methodological aspects such as non-invasive monitoring of visceromotor response to colorectal distension as being essential in successful identification and evaluation of novel therapeutic targets aimed at reducing stress-related alterations in visceral sensitivity. Underlying mechanisms of stress-induced modulation of visceral pain involve a combination of peripheral, spinal and supraspinal sensitization based on the nature of the stressors and dysregulation of descending pathways that modulate nociceptive transmission or stress-related analgesic response. PMID:21860814

  15. Altering the sex determination pathway in Drosophila fat body modifies sex-specific stress responses

    PubMed Central

    Neckameyer, Wendi S.

    2014-01-01

    The stress response in Drosophila melanogaster reveals sex differences in behavior, similar to what has been observed in mammals. However, unlike mammals, the sex determination pathway in Drosophila is well established, making this an ideal system to identify factors involved in the modulation of sex-specific responses to stress. In this study, we show that the Drosophila fat body, which has been shown to be important for energy homeostasis and sex determination, is a dynamic tissue that is altered in response to stress in a sex and time-dependent manner. We manipulated the sex determination pathway in the fat body via targeted expression of transformer and transformer-2 and analyzed these animals for changes in their response to stress. In the majority of cases, manipulation of transformer or transformer-2 was able to change the physiological output in response to starvation and oxidative stress to that of the opposite sex. Our data also uncover the possibility of additional downstream targets for transformer and transformer-2 that are separate from the sex determination pathway and can influence behavioral and physiological responses. PMID:24789992

  16. Red blood cells in Rett syndrome: oxidative stress, morphological changes and altered membrane organization.

    PubMed

    Ciccoli, Lucia; De Felice, Claudio; Leoncini, Silvia; Signorini, Cinzia; Cortelazzo, Alessio; Zollo, Gloria; Pecorelli, Alessandra; Rossi, Marcello; Hayek, Joussef

    2015-11-01

    In this review, we summarize the current evidence on the erythrocyte as a previously unrecognized target cell in Rett syndrome, a rare (1:10 000 females) and devastating neurodevelopmental disorder caused by loss-of-function mutations in a single gene (i.e. MeCP2, CDKL5, or rarely FOXG1). In particular, we focus on morphological changes, membrane oxidative damage, altered membrane fatty acid profile, and aberrant skeletal organization in erythrocytes from patients with typical Rett syndrome and MeCP2 gene mutations. The beneficial effects of ω-3 polyunsaturated fatty acids (PUFAs) are also summarized for this condition to be considered as a 'model' condition for autism spectrum disorders.

  17. Maternal separation is associated with strain-specific responses to stress and epigenetic alterations to Nr3c1, Avp, and Nr4a1 in mouse

    PubMed Central

    Kember, R L; Dempster, E L; Lee, T H A; Schalkwyk, L C; Mill, J; Fernandes, C

    2012-01-01

    Stressful events early in life have been widely linked to behavioral phenotypes and have been implicated in the development of psychiatric disorders. Using a maternal separation paradigm, we investigated phenotypic and epigenetic changes following early life stress in two inbred strains of mice, C57BL/6J and DBA/2J. We found an increase in the corticosterone response to stress in male, C57BL/6J mice that had undergone maternal separation compared to controls. In addition, early life stress induced a number of mild but significant behavioral changes, many of which were sex and strain dependent. Following maternal separation anxiety was decreased in males but increased in DBA/2J females, DBA/2J males displayed reduced exploration of a novel object, and baseline activity was altered in males of both strains. Finally, we examined DNA methylation levels in the hippocampus across promoter regions of Nr3c1, Avp, and Nr4a1, and found altered levels at several CpG sites in maternally separated male mice compared to controls. This study contributes to a growing body of recent literature suggesting that epigenetic changes may mediate the impact of early life stress on behavior. In particular, we establish that the phenotypic and epigenetic responses to an adverse environment differ as a function of genetic background. PMID:22950049

  18. Stress modulation of drug self-administration: implications for addiction comorbidity with post-traumatic stress disorder.

    PubMed

    Logrip, Marian L; Zorrilla, Eric P; Koob, George F

    2012-02-01

    Drug abuse and dependence present significant health burdens for our society, affecting roughly 10% of the population. Stress likely contributes to the development and persistence of drug use; for example, rates of substance dependence are elevated among individuals diagnosed with post-traumatic stress disorder (PTSD). Thus, understanding the interaction between stress and drug use, and associated neuroadaptations, is key for developing therapies to combat substance use disorders. For this purpose, many rodent models of the effects of stress exposure on substance use have been developed; the models can be classified according to three categories of stress exposure: developmental, adult nonsocial, and adult social. The present review addresses preclinical findings on the effect of each type of trauma on responses to and self-administration of drugs of abuse by focusing on a key exemplar for each category. In addition, the potential efficacy of targeting neuropeptide systems that have been implicated in stress responses and stress system neuroadaptation in order to treat comorbid PTSD and substance abuse will be discussed. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.

  19. Directed forgetting in post-traumatic-stress-disorder: a study of refugee immigrants in Germany.

    PubMed

    Baumann, Michaela; Zwissler, Bastian; Schalinski, Inga; Ruf-Leuschner, Martina; Schauer, Maggie; Kissler, Johanna

    2013-01-01

    People with post-traumatic stress disorder (PTSD) often suffer from memory disturbances. In particular, previous studies suggest that PTSD patients perform atypically on tests of directed forgetting, which may be mediated by an altered emotional appraisal of the presented material. Also, a special role of dissociative symptoms in traumatized individuals' memory performance has been suggested. Here, we investigate these issues in traumatized immigrants in Germany. In an item-method directed forgetting task, pictures were presented individually, each followed by an instruction to either remember or forget it. Later, recognition memory was tested for all pictures, regardless of initial instruction. Overall, the PTSD group's discrimination accuracy was lower than the control group's, as PTSD participants produced fewer hits and more false alarms, but the groups did not differ in directed forgetting itself. Moreover, the more negatively participants evaluated the stimuli, the less they were able to discriminate old from new items. Participants with higher dissociation scores were particularly poor at recognizing to-be-forgotten items. Results confirm PTSD patients' general discrimination deficits, but provide no evidence for a distinct directed forgetting pattern in PTSD. Furthermore, data indicate that, in general, more negatively perceived items are discriminated with less accuracy than more positively appraised ones. Results are discussed in the larger context of emotion and stress-related modulations of episodic memory, with particular focus on the role of dissociative symptoms.

  20. Post-traumatic stress disorder and memory: prescient medicolegal testimony at the International War Crimes Tribunal?

    PubMed

    Sparr, Landy F; Bremner, J Douglas

    2005-01-01

    The nature of remembrance of traumatic events has been particularly controversial during the past decade as vigorous new research has reshaped thinking about trauma and memory. Memory alterations in traumatized individuals have been investigated within both theoretical and biological frameworks. There are different types of memory, and empirical studies have associated post-traumatic stress disorder (PTSD) with a simultaneous weakening and a strengthening of memory. Memory deficiencies in PTSD have been found to be related to problems in new learning (explicit memory), but other specific deficiencies are unvalidated. Recently, accuracy of memory has received particular scrutiny because considerable importance is attached to victims' recollections. In 1998, at the International War Crimes Tribunal in The Hague, The Netherlands, a Bosnian-Croatian soldier was tried for aiding and abetting the rape of a Muslim woman. The defendant's lawyers suggested that the woman's memory was inaccurate, having been adversely affected by her traumatic experiences, and that the defendant whom she identified was not present during her interrogation and abuse. The prosecution disagreed and argued that memories of traumatic experiences in individuals with PTSD are characteristically hyperaccessible. Expert witnesses on both sides were brought in to provide medicolegal testimony about the scientific parameters of stress and its long-term effects on brain regions associated with memory. With the expert witness discussion as background, this article reviews the most recent research about the nature of memory in the aftermath of trauma and the politics of psychological trauma and the law.

  1. Environmental prenatal stress alters sexual dimorphism of maternal behavior in rats.

    PubMed

    Pérez-Laso, Carmen; Segovia, Santiago; Martín, José Luis R; Ortega, Esperanza; Gómez, Francisco; Del Cerro, M Cruz R

    2008-03-05

    The prenatal external environment can affect fetuses, altering the maternal behavior that they express when mature. In the present study, environmental prenatal stress (EPS) was applied to pregnant rats in their final week of gestation, and when their female offspring reached maturity, the long latency effect of the stress on those offspring was ascertained on their induced maternal behavior (MB), accessory olfactory bulb (AOB) morphology and plasma levels of ACTH and corticosterone (Cpd B). EPS reduced: the percentage of these virgins that showed induced MB, their retrieval of foster pups, the time spent crouching, and the quality of nest building; it also increased the incidence of their cannibalism of foster pups. The EPS-treated females presented a male-like pattern of induced MB. They showed increased plasma levels of ACTH and Cpd B and increased numbers of mitral cells in the AOB. These findings provide evidence that stress applied to the pregnant rat produces long-lasting behavioral, neuroanatomical and hormonal alterations in the female offspring that can be observed when they reach maturity.

  2. Maternal stress alters endocrine function of the feto-placental unit in rats.

    PubMed

    Mairesse, Jérôme; Lesage, Jean; Breton, Christophe; Bréant, Bernadette; Hahn, Tom; Darnaudéry, Muriel; Dickson, Suzanne L; Seckl, Jonathan; Blondeau, Bertrand; Vieau, Didier; Maccari, Stefania; Viltart, Odile

    2007-06-01

    Prenatal stress (PS) can cause early and long-term developmental effects resulting in part from altered maternal and/or fetal glucocorticoid exposure. The aim of the present study was to assess the impact of chronic restraint stress during late gestation on feto-placental unit physiology and function in embryonic (E) day 21 male rat fetuses. Chronic stress decreased body weight gain and food intake of the dams and increased their adrenal weight. In the placenta of PS rats, the expression of glucose transporter type 1 (GLUT1) was decreased, whereas GLUT3 and GLUT4 were slightly increased. Moreover, placental expression and activity of the glucocorticoid "barrier" enzyme 11beta-hydroxysteroid dehydrogenase type 2 was strongly reduced. At E21, PS fetuses exhibited decreased body, adrenal pancreas, and testis weights. These alterations were associated with reduced pancreatic beta-cell mass, plasma levels of glucose, growth hormone, and ACTH, whereas corticosterone, insulin, IGF-1, and CBG levels were unaffected. These data emphasize the impact of PS on both fetal growth and endocrine function as well as on placental physiology, suggesting that PS could program processes implied in adult biology and pathophysiology.

  3. Alterations in brain morphology and HSP70 expression in lizard embryos exposed to thermal stress.

    PubMed

    Simoniello, Palma; Esposito, Maria Grazia; Trinchella, Francesca; Motta, Chiara Maria; Scudiero, Rosaria

    2016-01-01

    The teratogenic effects of thermal stress were studied in the oviparous Italian wall lizard Podarcis sicula. To this purpose, the eggs were exposed to continuous or temporary cold (15°C) or warm (30°C) stresses and the effects were analysed at the cytological and molecular levels. The results demonstrated the lethality of the continuous regimes and of t