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Poster Session I, December 4, 2017

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Poster Session I, December 4, 2017 Neuropsychopharmacology (2017) 42, S111–S293 © 2017 American College of Neuropsychopharmacology. All rights reserved 0893-133X/17 www.neuropsychopharmacology.org Poster Session I Methods: We recruited a sample of (N = 63) African- Palm Springs, California, December 3-7, 2017 American women with T2DM and high rates of lifetime trauma exposure from the primary care and diabetes Sponsorship Statement: Publication of this supplement is specialty clinic waiting rooms of Grady Memorial Hospital, sponsored by the ACNP. a large county hospital and level 1 trauma center in Atlanta, Individual contributor disclosures may be found within the Georgia. PTSD diagnosis and PTSD symptom severity were abstracts. Part 1: All Financial Involvement with a pharma- determined using the Clinician-Administered PTSD Scale ceutical or biotechnology company, a company providing (CAPS). A fasting blood sample was collected and a study clinical assessment, scientific, or medical products or compa- physician performed a general medical assessment for each nies doing business with or proposing to do business with participant. Blood was assayed for hemoglobin A1c (HbA1c) ACNP over past 2 years (Calendar Years 2014–Present); Part and calculation of average estimated glucose (AEG) con- 2: Income Sources & Equity of $10,000 per year or greater centrations. Peripheral blood mononuclear cells (PBMCs) (Calendar Years 2014 - Present): List those financial relation- were extracted and assayed for nuclear factor-κB (NF-κB) ships which are listed in part one and have a value greater than pathway activity and monocyte glucocorticoid sensitivity $10,000 per year, OR financial holdings that are listed in part (expressed as dexamethasone [DexIC50]) using previously one and have a value of $10,000 or greater as of the date of validated methods. disclosure; Part 3: Financial Involvement with a pharmaceu- Results: Women with current PTSD had significantly tical or biotechnology company, a company providing clinical higher levels of HbA1c (p = 0.006) and AEG (p = 0.008) assessment, scientific, or medical products or companies doing compared to women without PTSD. Furthermore, business with or proposing to do business with ACNP which DexIC50 (p = 0.003) and NF-κB pathway activity constitutes more than 5% of personal income (Calendar Years (p = 0.013) were increased significantly in women with 2014 - Present); Part 4: Grants from pharmaceutical or PTSD as compared to women without PTSD. PTSD biotechnology company, a company providing clinical assess- symptom severity was predictive of higher DexIC50 ment, scientific, or medical products directly, or indirectly (r = 0.27; p = 0.05), denoting decreased glucocorticoid sensi- through a foundation, university, or any other organization tivity), higher HbA1c (r = 0.28; p = 0.024), higher AEG (Calendar Years 2014 - Present); Part 5: My primary employer (r = 0.27; p = 0.033), and higher NF-κB pathway activity is a pharmaceutical/biotech/medical device company. (r = 0.38; p = 0.023). Increased NF-κB pathway activity was Asterisks in the author lists indicate presenter of the abstract associated with higher HbA1c (r = 0.34; p = 0.05), but not at the annual meeting. with DexIC50 (r = 0.023; p = 0.91). Conclusions: PTSD diagnosis and PTSD symptom severity are positively associated with worsened glycemic regulation M1. Alterations in Glucocorticoid, Immune, and Meta- in African-American women with T2DM. In addition, PTSD bolic Regulation are Associated With Post-Traumatic diagnosis and PTSD symptom severity are also positively Stress Disorder in African-American Women With Type associated with increased monocyte glucocorticoid resistance II Diabetes Mellitus and increased innate immune activity. These data suggest mechanisms of shared pathophysiology and risk connecting Charles Gillespie*, Drew Dixon, Rachel Gluck, PTSD and T2DM which are both significant public health Adam Munoz, Hadrian Mendoza, Cleo Rochat, problems. Increased understanding of shared pathophysiol- Sierra Carter, Tanja Jovanovic, Negar Fani, ogy between stress-related psychiatric and medical disorders Abigail Lott, Bekh Bradley, Kerry Ressler, such as PTSD and T2DM may lead to novel approaches to Guillermo Umpierrez, Ann Schwartz, Thaddeus Pace, prevention and progression of disease and argues for Vasiliki Michopoulos improved integration of care for psychiatric and medical Emory University School of Medicine, Atlanta, Georgia, disorders. United States Keywords: Post-Traumatic Stress Disorder, Type-2 Diabetes, Women, Innate Immunity, Neuroendocrine Background: Post-traumatic stress disorder (PTSD) is a Disclosure: Nothing to Disclose. stress-related psychiatric disorder that is associated with increased risk for type 2 diabetes mellitus (T2DM). However, the biological mechanisms by which PTSD increases risks for M2. The Endogenous Hallucinogen N,N-Dimethyltryp- T2DM remain unclear. A growing body of data suggests that tamine Displays Protective Effects Against Hypoxia in dysregulation of the stress axis, including altered glucocorti- Cultured Human Cortical Neurons and Glial-Like Cells coid sensitivity and innate immune activity, may act to and Protects Against Renal Ischemia-Reperfusion Injury disrupt glycemic control in trauma-exposed individuals with Ede Frecska*, Attila Szabo PTSD. To evaluate the association between PTSD, glycemic regulation, neuroendocrine function and immune activity, University of Debrecen, Debrecen, Hungary we examined associations between PTSD diagnosis and PTSD symptom severity and metabolic, glucocorticoid, and Background: N,N-dimethyltryptamine (DMT) is a immune biomarkers in trauma-exposed women with T2DM. potent endogenous hallucinogen present in the mammalian ACNP 56th Annual Meeting Abstracts S112 brain. Recently, DMT has been found to activate the elevated plasma levels of inflammatory cytokines in alco- sigma-1 receptor (Sig-1 R), an intracellular chaperone holics. Here we tested the hypothesis that inflammation, as fulfilling an interface role between the endoplasmic measured by CRP, may interact with PTSD symptoms to reticulum and mitochondria. It ensures signaling of en- predict alcohol dependence behaviors. doplasmic reticulum overload into the nucleus resulting in Methods: In a study of combat trauma in active duty service the enhanced production of antistress and antioxidant members (Marine Resiliency Study), Marines and Navy proteins. Based on its central cellular role the activation of Corpsmen (N = 1890) were given the AUD Identification Sig-1 R can mitigate the outcome of hypoxia or oxidative Test (AUDIT) as well as the Clinician Administered PTSD stress and helps cell survival by attenuating endoplasmic Scale (CAPS) 3 months after a combat deployment to reticulum stress. Afghanistan or Iraq. AUDIT scores were totaled separately Methods: The first aim was to test the hypothesis that DMT for alcohol consumption (i.e. frequency and quantity of plays a protective role in the brain by activating the Sig-1 R. ‘ ’ drinking) and dependence behaviors (i.e. difficulty control- We tested in vitro whether DMT can alleviate hypoxic stress ling drinking and functional impairment). Plasma was (under 0.5% O2) in cultured human cortical neurons derived collected for measurement of CRP by enzyme-linked from induced pluripotent stem cells, monocyte-derived immunosorbent assay. Associations between PTSD, AUD, macrophages, and dendritic cells. The second aim was to and CRP at 3-month post-deployment were analyzed using investigate ‘in vivo’ the protective role of DMT in renal ischemia-reperfusion injury of rats after clamping of the left linear regression or zero-inflated negative binomial regres- renal artery and vein for up to 120 min. sion (ZINBR), to account for skewing from an excess in zero Results: Findings showed that DMT robustly increases the responses in the AUDIT score. Results: While a PTSD diagnosis predicted alcohol con- survival of the cultured cell types in severe hypoxia through N = β = po the Sig-1 R. Furthermore, this phenomenon is associated sumption ( 1446; 0.07, 0.01), there were no main with the decreased expression of the hypoxia-inducible factor effects of CRP or interactions. PTSD diagnosis predicted a 1-alpha (HIF-1 A) suggesting that DMT may alleviate roughly 10% lower chance of not demonstrating any hypoxic stress and increase cell survival in an HIF-1 A- dependence behavior (N = 1446, β = 0.98, po0.001, ZINBR independent manner. Pretreatment of rats with DMT zero model). In those endorsing dependence symptoms, improved red blood cell deformability, renal function, and PTSD diagnosis alone did not predict dependence severity tissue morphology after 30-60-120 minutes of renal but did interact with CRP to predict dependence severity ischemia-reperfusion injury. (N = 353, β = 0.24, po0.02, count model regression), with Conclusions: Our results reveal a novel and important role of increasing CRP associated with increased dependence DMT in human cellular physiology. We postulate that this symptoms only in the PTSD group. Similar findings were compound may ameliorate the adverse effects of hypoxic/ found using total CAPS severity scores instead of PTSD ischemic insult to the brain and other organs. diagnosis. It should be noted that of those reporting at least Keywords: Dimethyltryptamine, Hypoxia, Ischemia- some dependence behaviors (40), symptom severity in Reperfusion Injury, Sigma-1 Receptor subjects with PTSD was 2.51 (range = 1-11) and those Disclosure: Nothing to Disclose. without PTSD averaged 2.37 (range
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