Predator Exposure/Psychosocial Stress Animal Model of Post-Traumatic Stress Disorder Modulates Neurotransmitters in the Rat Hippocampus and Prefrontal Cortex

Post-Traumatic Stress Disorder (PTSD) can develop in response to a traumatic event involving a threat to life. To date, no diagnostic biomarkers have been identified for PTSD. Recent research points toward physiological abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis, sympathoadrenal medullary and immune system that may be implicated in the disorder. The modulation of neurotransmitters is another possible mechanism, but their role in the progression of PTSD is poorly understood. Low serotonin (5-HT) may be a factor, but it may not be the only neurotransmitter affected as modulation affects levels of other neurotransmitters. In this study, we hypothesized the predator exposure/psychosocial stress rodent model of PTSD may alter levels of 5-HT and other neurotransmitters in the rat hippocampus and prefrontal cortex (PFC). Male Sprague-Dawley rats were used in this experiment. We induced PTSD via a predator exposure/psychosocial stress model, whereby rats were placed in a cage with a cat for 1 hour on days 1 and 11 of the 31-day experiment. Rats also received psychosocial stress via daily cage cohort changes. On day 32, the rats were sacrificed and the brains dissected to remove the hippocampus and PFC. Norepinephrine (NE), 5-Hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), dopamine (DA), and 3,4-Dihydroxyphenylacetic acid (DOPAC), and 5-HT levels in the hippocampus and PFC were measured with high-performance liquid chromatography (HPLC). In the hippocampus, 5-HT and HVA were lower, while NE and DOPAC were higher, in the PTSD group vs. controls. In the PFC, only 5-HT was lower, while NE, DA, and DOPAC were higher, in the PTSD group vs. controls. The rate limiting enzymes tyrosine hydroxylase and tryptophan hydroxylase were also examined and confirmed our findings. These results demonstrate that the predator exposure/psychosocial stress model of PTSD produces neurotransmitter changes similar to those seen in human patients and may cause a heightened noradrenergic response

Inflammation and Oxidative Stress Are Elevated in the Brain, Blood, and Adrenal Glands during the Progression of Post-Traumatic Stress Disorder in a Predator Exposure Animal Model

This study sought to analyze specific pathophysiological mechanisms involved in the progression of post-traumatic stress disorder (PTSD) by utilizing an animal model. To examine PTSD pathophysiology, we measured damaging reactive oxygen species and inflammatory cytokines to determine if oxidative stress and inflammation in the brain, adrenal glands, and systemic circulation were upregulated in response to constant stress. Pre-clinical PTSD was induced in naïve, male Sprague-Dawley rats via a predator exposure/psychosocial stress regimen. PTSD group rats were secured in Plexiglas cylinders and placed in a cage with a cat for one hour on days 1 and 11 of a 31-day stress regimen. In addition, PTSD group rats were subjected to psychosocial stress whereby their cage cohort was changed daily. This model has been shown to cause heightened anxiety, exaggerated startle response, impaired cognition, and increased cardiovascular reactivity, all of which are common symptoms seen in humans with PTSD. At the conclusion of the predator exposure/psychosocial stress regimen, the rats were euthanized and their brains were dissected to remove the hippocampus, amygdala, and pre-frontal cortex (PFC), the three areas commonly associated with PTSD development. The adrenal glands and whole blood were also collected to assess systemic oxidative stress. Analysis of the whole blood, adrenal glands, and brain regions revealed oxidative stress increased during PTSD progression. In addition, examination of pro-inflammatory cytokine (PIC) mRNA and protein demonstrated neurological inflammatory molecules were significantly upregulated in the PTSD group vs. controls. These results indicate oxidative stress and inflammation in the brain, adrenal glands, and systemic circulation may play a critical role in the development and further exacerbation of PTSD. Thus, PTSD may not be solely a neurological pathology but may progress as a systemic condition involving multiple organ systems

Prevalence, overlap, and predictors of functional somatic syndromes in a student sample

Background Although at least 20 different functional somatic syndromes (FSS) have been described, and overlaps between individual FSS and a high comorbidity with depressive and anxiety disorders have been suggested, barely any studies have examined a broad array of FSS within one study. Moreover, information on psychosocial risk factors gained from prospective studies is scarce. Purpose This study aimed to determine prevalence rates, overlap, and comorbidity in 17 FSS and to estimate the influence of psychosocial risk factors on the development of FSS. Methods In total, 3,054 students (73.4 % women) completed a Web survey containing questions on FSS, comorbidity, and psychosocial risk factors at baseline. Of these, 429 completed the survey again 6 months later. Results The prevalence of any FSS was 9.5 %, with 227 (78.6 %) subjects fulfilling criteria for only one FSS, 49 (17.0 %) reporting two, and 12 (4.2 %) reporting three syndromes simultaneously. Only one person suffered from four FSS at the same time. “Major depressive syndrome” (15.6 %), “panic syndrome” (4.8 %), and “other anxiety syndromes” (19.7 %) frequently occurred among persons with FSS. Significant predictors of FSS were number of somatic symptoms (OR = 1.15), impairment in daily activities (OR = 3.17), depression (OR = 1.13), and somatization (OR = 1.15). Conclusions Our findings indicate that FSS are common in nonclinical samples. The frequency of overlap and comorbidity in FSS was lower compared with previous research. A consideration of psychosocial risk factors is warranted in the prevention and management of FSS