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.

Hospitalization for physical injury may contribute to recovery of invisible war wounds: Response to Peterson's (2021) commentary on Soumoff et al. (2021).

Peterson's (2021) commentary on our recently published manuscript (Soumoff et al., 2021) suggests that our findings are an example of visible, physical injuries of war facilitating communication with others, which, in turn, fosters recovery from invisible war wounds. We agree that in the proper context, the retelling of one's traumatic story can be important for recovery from and, perhaps, even the prevention of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). Participants in our study cohort differed from most others who experienced combat trauma in that while they were hospitalized, they experienced nearly daily visits from a behavioral health provider to address traumatic stress-related symptoms. It is likely that individuals who sustained more severe physical injury (i.e., higher Injury Severity Score [ISS] ratings) had longer hospital stays, received more support, and had more opportunities to retell their stories than those with less severe injuries, leading to decreases in PTSD and MDD symptoms. To note support of this supposition, in Table 5 of Soumoff et al. (2021), although not significant, the adjusted odds ratios (aORs) for PTSD and MDD were below 1 for service members with high (i.e., above 16) ISS ratings. The physical injury-related hospitalizations participants in our sample experienced fostered activities described by Peterson (2021) that likely contributed to the prevention and resolution of PTSD and MDD symptoms, benefits not received by most individuals who suffer only invisible wounds of war.

Effects of subanesthetic intravenous ketamine infusion on neuroplasticity-related proteins in the prefrontal cortex, amygdala, and hippocampus of Sprague-Dawley rats.

Ketamine, a multimodal dissociative anesthetic, is a powerful analgesic administered following trauma due to its hemodynamic and respiratory stability. However, ketamine can cause hallucination and dissociation which may adversely impact traumatic memory after an injury. The effects of ketamine on proteins implicated in neural plasticity are unclear due to different doses, routes, and timing of drug administration in previous studies. Here, we investigated the effects of a single intravenous (IV) ketamine infusion on protein levels in three brain regions of rats. Adult male Sprague-Dawley rats with indwelling IV catheters underwent an auditory fear conditioning (three pairings of tone and mild footshock 0.8 mA, 0.5 s) and received a high dose of IV ketamine (0 or 40 mg/kg/2 h) infusion (Experiment 1). In a follow-up study, animals received a low dose of IV ketamine (0 or 10 mg/kg/2 h) infusion (Experiment 2). Two hours after the infusion, brain tissue from the medial prefrontal cortex (mPFC), hippocampus, and amygdala were collected for western blot analyses. Protein levels of a transcription factor (c-Fos), brain-derived neurotrophic factor (BDNF), and phosphorylated extracellular signal-regulated kinase (pERK) were quantified in these regions. The 40 mg/kg ketamine infusion increased c-Fos levels in the mPFC and amygdala as well as pERK levels in the mPFC and hippocampus. The 10 mg/kg ketamine infusion increased BDNF levels in the amygdala, but decreased pERK levels in the mPFC and hippocampus. These findings suggest that a clinically relevant route of ketamine administration produces dose-dependent and brain region-specific effects on proteins involved in neuroplasticity.

Enhanced fear memories and brain glucose metabolism (18F-FDG-PET) following sub-anesthetic intravenous ketamine infusion in Sprague-Dawley rats.

Ketamine is a multimodal dissociative anesthetic, which provides powerful analgesia for victims with traumatic injury. However, the impact of ketamine administration in the peri-trauma period on the development of post-traumatic stress disorder (PTSD) remains controversial. Moreover, there is a major gap between preclinical and clinical studies because they utilize different doses and routes of ketamine administration. Here, we investigated the effects of sub-anesthetic doses of intravenous (IV) ketamine infusion on fear memory and brain glucose metabolism (BGluM) in rats. Male Sprague-Dawley rats received an IV ketamine infusion (0, 2, 10, and 20 mg/kg, 2 h) or an intraperitoneal (IP) injection (0 and 10 mg/kg) following an auditory fear conditioning (3 pairings of tone and foot shock [0.6 mA, 1 s]) on day 0. Fear memory retrieval, fear extinction, and fear recall were tested on days 2, 3, and 4, respectively. The effects of IV ketamine infusion (0 and 10 mg/kg) on BGluM were measured using 18F-fluoro-deoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT). The IV ketamine infusion dose-dependently enhanced fear memory retrieval, delayed fear extinction, and increased fear recall in rats. The IV ketamine (10 mg/kg) increased BGluM in the hippocampus, amygdala, and hypothalamus, while decreasing it in the cerebellum. On the contrary, a single ketamine injection (10 mg/kg, IP) after fear conditioning facilitated fear memory extinction in rats. The current findings suggest that ketamine may produce differential effects on fear memory depending on the route and duration of ketamine administration.