Corticotropin-Releasing Factor, Interleukin-6, Brain-Derived Neurotrophic Factor, Insulin-Like Growth Factor-1, and Substance P in the Cerebrospinal Fluid of Civilians With Posttraumatic Stress Disorder Before and After Treatment With Paroxetine
ABSTRACT Posttraumatic stress disorder (PTSD) is associated with altered concentrations of stress-related neurohormones, neurotrophins, and neuropeptides in plasma and serum; however, few studies have examined central alterations of these measures in individuals with PTSD. Furthermore, no study to date has evaluated the effects of successful antidepressant treatment on cerebrospinal fluid (CSF) abnormalities in PTSD.
Sixteen medication-free outpatients with chronic PTSD (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) due to physical and/or sexual abuse or motor vehicle accidents (mean ± SD age = 36 ± 11.4 years, 12 women) and 11 nontraumatized healthy subjects (mean ± SD age = 35.3 ± 13.1 years, 7 women) underwent a lumbar puncture for collection of CSF. Seven PTSD patients had a repeat lumbar puncture 12 weeks later, after successful treatment of PTSD with paroxetine. CSF was analyzed for corticotropin-releasing factor (CRF), interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and substance P concentrations. The study was conducted between January 2003 and August 2004.
Compared to nontraumatized healthy controls, patients with chronic PTSD had similar pretreatment concentrations of CSF CRF, IL-6, BDNF, IGF-1, and substance P. Posttreatment CSF measures did not change significantly in patients whose symptoms remitted with paroxetine.
Chronic, moderate PTSD due to civilian trauma, without psychotic symptoms and without significant rates of comorbid depression, alcohol dependence, or substance dependence, is not associated with abnormalities in CSF CRF, IL-6, BDNF, IGF-1, or substance P levels. Despite substantial reduction in PTSD symptoms, antidepressant treatment does not alter normal central concentrations of these neurochemicals, with the possible exception of substance P.
- SourceAvailable from: I.L. Torres
[Show abstract] [Hide abstract]
- "In some studies, BDNF is used as a biological marker of clinical conditions such as anxiety, depression, fibromyalgia, and schizophrenia (Kurita et al., 2012; Nurjono et al., 2012). However, the relationship between BDNF levels and anxiety disorders is controversial: BDNF levels appear to be either reduced increased, or not significantly altered in patients with anxiety disorders (Bonne et al., 2011; Dell'Osso et al., 2009; Dos Santos et al., 2011; Molendijk et al., 2012; Wang et al., 2011). In an animal study, using genetically engineered mice for BDNF overexpression resulted in elevated anxiety (Govindarajan et al., 2006). "
ABSTRACT: Neuropathic pain (NP) is a chronic pain modality that usually results of damage in the somatosensory system. NP often shows insufficient response to classic analgesics and remains a challenge to medical treatment. The Transcranial Direct Current Stimulation (tDCS) is a non-invasive technique, which induces neuroplastic changes in central nervous system of animals and humans. The brain derived neurotrophic factor plays an important role in synaptic plasticity process. Behavior changes such as decreased locomotor and exploratory activities and anxiety disorders are common comorbidities associated with NP. Evaluate the effect of tDCS treatment on locomotor and exploratory activities, and anxiety-like behavior, and peripheral and central BDNF levels in rats submitted to neuropathic pain model. Rats were randomized divided: Ss, SsS, SsT, NP, NpS, NpT. The neuropathic pain model was induced by partial sciatic nerve compression at 14days after surgery; the tDCS treatment was initiated. The animals of treated groups were subjected to a 20minutes session of tDCS, for eight days. The Open Field and Elevated Pluz Maze tests were applied after 24hours (phase I) and 7days (phase II) the end of tDCS treatment. The serum, spinal cord, brainstem and cerebral cortex BDNF levels were determined 48hours (phase I) and 8days (phase II) after tDCS treatment by (ELISA). The chronic constriction injury (CCI)2 induces decrease in locomotor and exploratory activities, increases in the behavior-like anxiety, and increases in the brainstem BDNF levels, the last, in the phase II (one-way ANOVA/SNK, P<0.05 for all). Already, the tDCS treatment reverted all these effects induced by CCI (one-way ANOVA/SNK, P<0.05 for all). Furthermore, the tDCS treatment decreased serum and cerebral cortex BDNF levels and it increased these levels in the spinal cord in phase II (one-way ANOVA/SNK, P<0.05). tDCS reverts behavioral alterations associated to neuropathic pain, indicating possible analgesic and anxiolytic tDCS effects. tDCS treatment induces changes in the BDNF levels in different regions of the central nervous system (CNS), and this effect can be attributed to different cellular signaling activations. Copyright © 2015. Published by Elsevier Inc.Progress in Neuro-Psychopharmacology and Biological Psychiatry 07/2015; DOI:10.1016/j.pnpbp.2015.06.016 · 4.03 Impact Factor
[Show abstract] [Hide abstract]
- "Several studies have reported significantly higher mean concentrations of various pro-inflammatory cytokines in serum (Guo et al., 2012; Hoge et al., 2009; Maes et al., 1999; Spitzer et al., 2010; Spivak et al., 1997; Tucker et al., 2004) and in cerebrospinal fluid (CSF) (Baker et al., 2001) of individuals with PTSD, although not all studies are in agreement (Bonne et al., 2011; Kawamura et al., 2001; McCanlies et al., 2011). Possible sources of discrepancy across studies include small sample sizes and the failure to account for the potential confounding effects of comorbid Major Depressive Disorder (MDD) and early life trauma, all of which are common in combat-related PTSD (Breslau et al., 1999; Gros et al., 2012; Kessler et al., 1995), and some of which may, themselves, be accompanied by elevations of pro-inflammatory cytokines (Lindqvist et al., 2009; Schiepers et al., 2005; Slopen et al., 2013). "
ABSTRACT: Background: Chronic inflammation may be involved in combat-related post-traumatic stress disorder (PTSD) and may help explain comorbid physical diseases. However, the extent to which combat exposure per se, depression, or early life trauma, all of which are associated with combat PTSD, may confound the relationship between PTSD and inflammation is unclear. Methods: We quantified interleukin (IL)-6, IL-1 beta, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and C-reactive protein (CRP) in 51 combat-exposed males with PTSD and 51 combat-exposed males without PTSD, and assessed PTSD and depression severity as well as history of early life trauma. To decrease the possibility of Type I errors, we summed standardized scores of IL-1 beta, IL-6, TNF alpha, IFN gamma and CRP into a total "pro-inflammatory score". PTSD symptom severity was assessed with the Clinician Administered PTSD Scale (CAPS) rating scale. Results: Subjects with PTSD had significantly higher pro-inflammatory scores compared to combat-exposed subjects without PTSD (p = 0.006), and even after controlling for early life trauma, depression diagnosis and severity, body mass index, ethnicity, education, asthma/allergies, time since combat and the use of possibly confounding medications (p = 0.002). Within the PTSD group, the pro-inflammatory score was not significantly correlated with depressive symptom severity, CAPS total score, or with the number of early life traumas. Conclusions: Combat-related PTSD in males is associated with higher levels of pro-inflammatory cytokines, even after accounting for depression and early life trauma. These results, from one of the largest studies of inflammatory cytokines in PTSD to date, suggest that immune activation may be a core element of PTSD pathophysiology more so than a signature of combat exposure alone. (C) 2014 Published by Elsevier Inc.Brain Behavior and Immunity 06/2014; 42. DOI:10.1016/j.bbi.2014.06.003 · 6.13 Impact Factor
[Show abstract] [Hide abstract]
- "However, so far fewer studies have investigated this neurotrophin in patients with PTSD. The only study exploring cerebrospinal fluid BDNF levels among patients with PTSD found no difference compared with healthy controls; however, the sample size was small, and comprised mostly of female civilians with moderate PTSD severity (Bonne et al., 2011). Dell'Osso et al. (2009) compared plasma BDNF levels among drug-naıve PTSD patients without psychiatric comorbidity and healthy subjects and found significantly lower BDNF levels in PTSD patients. "
ABSTRACT: Post-traumatic stress disorder (PTSD) is a syndrome resulting from exposure to a severe traumatic event that poses threatened death or injury and produces intense fear and helplessness. The neural structures implicated in PTSD development belong to the limbic system, an important region for emotional processing. Brain-derived neurotrophic factor (BDNF) is a neurotrophin that serves as survival factor for selected populations of central nervous system (CNS) neurons and plays a role in the limbic system by regulating synaptic plasticity, memory processes and behavior. Impaired BDNF production in the brain can lead to a variety of CNS dysfunctions including symptoms associated with PTSD. However, so far fewer studies have investigated this neurotrophin in patients with PTSD. Furthermore, given the multiple role of BDNF in various CNS disorders, it cannot be excluded that traumatic events per se may influence neurotrophin levels, without a direct association to the PTSD syndrome. To elucidate these issues, in this study we analyzed BDNF serum levels in two groups of subjects: patients with trauma exposure who developed PTSD, and subjects with trauma exposure who did not develop PTSD. We found that BDNF serum levels were lower in PTSD patients as compared to related control subjects. Thus, these data suggest that BDNF might be involved in pathophysiology of PTSD and consequently therapeutic approaches aimed at restoring BDNF serum levels may be beneficial to this pathology.Brain and Cognition 12/2013; 84(1):118-122. DOI:10.1016/j.bandc.2013.11.012 · 2.68 Impact Factor