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

Department of Psychiatry, Hadassah Hebrew University Medical Center, POB 12000, Jerusalem, Israel 91120.
The Journal of Clinical Psychiatry (Impact Factor: 5.5). 12/2010; 72(8):1124-8. DOI: 10.4088/JCP.09m05106blu
Source: PubMed


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.

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    • "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). "
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    Progress in Neuro-Psychopharmacology and Biological Psychiatry 07/2015; 64. DOI:10.1016/j.pnpbp.2015.06.016 · 3.69 Impact Factor
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    • "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). "
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    Brain Behavior and Immunity 06/2014; 42. DOI:10.1016/j.bbi.2014.06.003 · 5.89 Impact Factor
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    • "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. "
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    Brain and Cognition 12/2013; 84(1):118-122. DOI:10.1016/j.bandc.2013.11.012 · 2.48 Impact Factor
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