scholarly journals Hippocampal TNF-α Signaling Mediates Heroin Withdrawal-Enhanced Fear Learning and Withdrawal-Induced Weight Loss

Author(s):  
Shveta V. Parekh ◽  
Jacqueline E. Paniccia ◽  
Lydia O. Adams ◽  
Donald T. Lysle

AbstractThere is significant comorbidity of opioid use disorder (OUD) and post-traumatic stress disorder (PTSD) in clinical populations. However, the neurobiological mechanisms underlying the relationship between chronic opioid use and withdrawal and development of PTSD are poorly understood. Our previous work identified that chronic escalating heroin administration and withdrawal can produce enhanced fear learning, an animal model of hyperarousal, and is associated with an increase in dorsal hippocampal (DH) interleukin-1β (IL-1β). However, other cytokines, such as TNF-α, work synergistically with IL-1β and may have a role in the development of enhanced fear learning. Based on both translational rodent and clinical studies, TNF-α has been implicated in hyperarousal states of PTSD, and has an established role in hippocampal-dependent learning and memory. The first set of experiments tested the hypothesis that chronic heroin administration followed by withdrawal is capable of inducing alterations in DH TNF-α expression. The second set of experiments examined whether DH TNF-α expression is functionally relevant to the development of enhanced fear learning. We identified an increase of TNF-α immunoreactivity and positive cells at 0, 24, and 48 h into withdrawal in the dentate gyrus DH subregion. Interestingly, intra-DH infusions of etanercept (TNF-α inhibitor) 0, 24, and 48 h into heroin withdrawal prevented the development of enhanced fear learning and mitigated withdrawal-induced weight loss. Overall, these findings provide insight into the role of TNF-α in opioid withdrawal and the development of anxiety disorders such as PTSD.

BJPsych Open ◽  
2021 ◽  
Vol 7 (4) ◽  
Author(s):  
Tea Rosic ◽  
Vivian Y. O. Au ◽  
Andrew Worster ◽  
David C. Marsh ◽  
Lehana Thabane ◽  
...  

Background Exposure to traumatic events is both a risk factor for substance use and an adverse outcome of substance use disorders. Identifying and managing post-traumatic stress disorder (PTSD) in patients with addiction requires attention. Aims To examine the lifetime prevalence of traumatic events and past-month prevalence of PSTD in patients treated for opioid use disorder, and explore the association between trauma, PTSD and treatment outcomes. Method Participants (n = 674) receiving methadone treatment in 20 community clinics across Ontario, Canada, were administered the Mini-International Neuropsychiatric Interview to identify self-reported traumatic events and PTSD. Drug use was measured for 12 months by urine drug screens. Results Eleven per cent of participants met past-month criteria for PTSD (n = 72), and 48% reported history of traumatic events with no current PTSD (n = 323). Participants with PTSD were more likely to be female (odds ratio 2.13, 95% CI 1.20–3.76) and less likely to be employed (odds ratio 0.31, 95% CI 0.16–0.61) or married (odds ratio 0.51, 95% CI 0.26–0.90) than those with no trauma history. Antidepressants (39 v. 24%) and benzodiazepines (36 v. 18%) were differentially prescribed to patients with and without PTSD. Length of time in treatment and opioid use were not associated with trauma; however, suicidal ideation was more common in PTSD (odds ratio 2.29, 95% CI 1.04–5.01). Conclusions Trauma and PTSD are prevalent among patients with opioid use disorder, and consideration of trauma symptoms and associated characteristics is warranted. Patients with and without comorbid PTSD differ clinically and psychosocially, highlighting the relevance of integrating addiction and mental health services for this population.


2018 ◽  
Vol 8 (8) ◽  
pp. 73
Author(s):  
Rikinkumar Patel ◽  
Geetha Manikkara ◽  
Priya Patel ◽  
Jupi Talukdar ◽  
Zeeshan Mansuri

Objective: To analyze differences in demographic pattern and hospitalization outcomes in post-traumatic stress disorder (PTSD) with opioid use disorder (OUD) patients managed with versus without behavioral therapy (BT). Methods: We conducted case-control study using Nationwide Inpatient Sample and identified PTSD and OUD using ICD–9–CM codes. Linear regression model was used to evaluate impact of BT on inpatient stay and cost. Results: We analyzed 1531 inpatient admissions and 786 patients received BT. Females had higher odds of receiving BT during inpatient management for PTSD with OUD (OR 1.210; 95% CI 1.020–1.436). About 63.1% patients receiving BT were benefited by Medicaid. Patients receiving BT had an increase in hospital stay by 1.27 days (P = 0.085) and hospitalization cost by $4734 (P = 0.018). There were no transfers to short term hospitals and lower transfers to skilled nursing facility (3.8% vs. 10.1%) in patients receiving BT. Conclusion: This study aims to reinforce combination management with psychotropic medications and BT in PTSD patients with comorbid OUD during hospitalization as it significantly decreases adverse disposition of the patient and thereby improves the quality of life post-treatment.


AIDS Care ◽  
2021 ◽  
pp. 1-8
Author(s):  
Elenore Bhatraju ◽  
Jane M. Liebschutz ◽  
Sara Lodi ◽  
Leah S. Forman ◽  
Marlene C. Lira ◽  
...  

2021 ◽  
pp. 1-10
Author(s):  
Eric L. Garland ◽  
Spencer T. Fix ◽  
Justin P. Hudak ◽  
Edward M. Bernat ◽  
Yoshio Nakamura ◽  
...  

Abstract Background Neuropsychopharmacologic effects of long-term opioid therapy (LTOT) in the context of chronic pain may result in subjective anhedonia coupled with decreased attention to natural rewards. Yet, there are no known efficacious treatments for anhedonia and reward deficits associated with chronic opioid use. Mindfulness-Oriented Recovery Enhancement (MORE), a novel behavioral intervention combining training in mindfulness with savoring of natural rewards, may hold promise for treating anhedonia in LTOT. Methods Veterans receiving LTOT (N = 63) for chronic pain were randomized to 8 weeks of MORE or a supportive group (SG) psychotherapy control. Before and after the 8-week treatment groups, we assessed the effects of MORE on the late positive potential (LPP) of the electroencephalogram and skin conductance level (SCL) during viewing and up-regulating responses (i.e. savoring) to natural reward cues. We then examined whether these neurophysiological effects were associated with reductions in subjective anhedonia by 4-month follow-up. Results Patients treated with MORE demonstrated significantly increased LPP and SCL to natural reward cues and greater decreases in subjective anhedonia relative to those in the SG. The effect of MORE on reducing anhedonia was statistically mediated by increases in LPP response during savoring. Conclusions MORE enhances motivated attention to natural reward cues among chronic pain patients on LTOT, as evidenced by increased electrocortical and sympathetic nervous system responses. Given neurophysiological evidence of clinical target engagement, MORE may be an efficacious treatment for anhedonia among chronic opioid users, people with chronic pain, and those at risk for opioid use disorder.


Author(s):  
Elizabeth P. Bauer ◽  
Denis Paré

Normal fear regulation includes the ability to learn by experience that some circumstances predict danger. This process, which can be modeled in the laboratory using Pavlovian fear conditioning, appears to be disrupted in individuals with post-traumatic stress disorder (PTSD). Understanding of the mechanisms underlying fear learning has progressed tremendously in the last 25 years, and constitutes a promising paradigm to study the neural bases of PTSD. This chapter first reviews current knowledge of the brain structures involved in fear learning, expression and extinction, including the contributions of the amygdala and prefrontal cortex. It then addresses how these circuits are affected by PTSD and how fear processing is altered in PTSD. Understanding PTSD within a fear-conditioning and extinction framework provides insight into why certain individuals are susceptible to developing PTSD and suggests potential therapies.


Author(s):  
Mahshid Ataei ◽  
Farshad M. Shirazi ◽  
Roland J. Lamarine ◽  
Samaneh Nakhaee ◽  
Omid Mehrpour

AbstractToday, COVID-19 is spreading around the world. Information about its mechanism, prognostic factors, and management is minimal. COVID-19, as a human disease, has several identifying phases. Physicians of patients with COVID-19 may be interested in knowing whether opioid use disorder may affect their patients’ course or prognosis. This information may be crucial when considering the opioid epidemic in the US and other parts of the world. Opioid use at high doses and over several months duration can mitigate the immune system’s function, which may complicate the course of COVID-19 disease. Potential suppression of parts of the immune response may be important in prevention, clinical support, and therapeutic use of medications in various phases of the COVID-19. Specifically, opioid use disorders via an inhalation route may enhance the “late hyper-inflammatory phase” or result in end-organ damage. It is well established that opioids decrease ventilation as their effect on the medullary respiratory centers increases the risk of pneumonia. This increased risk has been associated with immune-suppressive opioids. The ultimate role of opioids in COVID-19 is not clear. This paper endorses the need for clinical studies to decipher the role and impact of chronic opioid use on viral diseases such as COVID-19.


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