Inflammation, stress and depression: An exploration of ketamine's therapeutic profile.

Well-established animal models of depression have described a proximal relationship between stress and central nervous system (CNS) inflammation - a relationship mirrored in the peripheral inflammatory biomarkers of individuals with depression. Evidence also suggests that stress-induced proinflammatory states can contribute to the neurobiology of treatment-resistant depression. Interestingly, ketamine, a rapid-acting antidepressant, can partially exert its therapeutic effects via anti-inflammatory actions on the hypothalamic-pituitary adrenal (HPA) axis, the kynurenine pathway or by cytokine suppression. Further investigations into the relationship between ketamine, inflammation and stress could provide insight into ketamine's unique therapeutic mechanisms and stimulate efforts to develop rapid-acting, anti-inflammatory-based antidepressants.

Somatic Symptom Severity, Not Injury Severity, Predicts Probable Posttraumatic Stress Disorder and Major Depressive Disorder in Wounded Service Members.

Although previous studies have reported an association between patient-reported somatic symptom severity and the development of posttraumatic stress disorder (PTSD) or major depressive disorder (MDD) in injured military service members (SMs), conclusions from other studies regarding the association between clinician-determined injury severity and PTSD or MDD remain unclear. The present study investigated whether somatic symptoms or injury severity predict the development of probable PTSD or MDD in wounded SMs medically evacuated from combat areas. Data including SM demographic characteristics, clinician-determined injury severity (i.e., Injury Severity Score [ISS] and Abbreviated Injury Scale [AIS] values), and self-report assessments of PTSD (PTSD Checklist-Civilian Version), MDD (Patient Health Questionnaire [PHQ]-9), and somatic symptoms (PHQ-15) were analyzed. A total of 2,217 SMs completed at least one self-assessment between 2003 and 2014, with 425 having completed assessments at each assessment period (AP), conducted 1-75 (AP1), 76-165 (AP2), and 166-255 (AP3) days postinjury. Between AP1 and AP3, the rates of probable PTSD and MDD increased from 3.0% to 11.7% and from 2.8% to 9.2%, respectively. Somatic symptom severity at AP1 predicted probable PTSD and MDD at all three APs, odds ratios (ORs) = 3.5-11.5; however, ISS values did not predict probable PTSD or MDD at any AP, ORs = 0.6-0.9. This suggests that the initial severity of self-reported somatic symptoms rather than clinician-determined injury severity predicts the development of probable PTSD and MDD in wounded SMs.