mdl-100907 and Stress-Disorders--Post-Traumatic

War is a tragic event and its mental health consequences can be profound. Recent studies indicate substantial rates of posttraumatic stress disorder and other behavioral alterations because of war exposure. Understanding the psychological, behavioral, and neurobiological mechanism of mental health and behavioral changes related to war exposure is critical to helping those in need of care. Substantial work to encourage bench to bedside to community knowledge and communication is a core component of addressing this world health need.

Topics: Afghan Campaign 2001-; Aggression; Amygdala; Animals; Annexin A2; Disasters; Fear; Gene Expression; Humans; Iraq War, 2003-2011; Military Personnel; Mortuary Practice; S100 Proteins; Serotonin 5-HT2 Receptor Antagonists; Stress Disorders, Post-Traumatic; Stress, Psychological; Substance-Related Disorders; Suicide; Suicide Prevention; United States; Violence; Warfare

Prior exposure to stress is a risk factor for developing posttraumatic stress disorder (PTSD) in response to trauma, yet the mechanisms by which this occurs are unclear. Using a rodent model of stress-based susceptibility to PTSD, we investigated the role of serotonin in this phenomenon.. Adult mice were exposed to repeated immobilization stress or handling, and the role of serotonin in subsequent fear learning was assessed using pharmacologic manipulation and western blot detection of serotonin receptors, measurements of serotonin, high-speed optogenetic silencing, and behavior.. Both dorsal raphe serotonergic activity during aversive reinforcement and amygdala serotonin 2C receptor (5-HT2CR) activity during memory consolidation were necessary for stress enhancement of fear memory, but neither process affected fear memory in unstressed mice. Additionally, prior stress increased amygdala sensitivity to serotonin by promoting surface expression of 5-HT2CR without affecting tissue levels of serotonin in the amygdala. We also showed that the serotonin that drives stress enhancement of associative cued fear memory can arise from paired or unpaired footshock, an effect not predicted by theoretical models of associative learning.. Stress bolsters the consequences of aversive reinforcement, not by simply enhancing the neurobiological signals used to encode fear in unstressed animals, but rather by engaging distinct mechanistic pathways. These results reveal that predictions from classical associative learning models do not always hold for stressed animals and suggest that 5-HT2CR blockade may represent a promising therapeutic target for psychiatric disorders characterized by excessive fear responses such as that observed in PTSD.

Topics: Amygdala; Animals; Association Learning; Conditioning, Psychological; Disease Models, Animal; Dorsal Raphe Nucleus; Electroshock; Fear; Male; Memory Consolidation; Mice, Inbred C57BL; Mice, Transgenic; Models, Neurological; Models, Psychological; Neurons; Optogenetics; Receptor, Serotonin, 5-HT2C; Restraint, Physical; Serotonin; Serotonin 5-HT2 Receptor Antagonists; Serotonin Plasma Membrane Transport Proteins; Stress Disorders, Post-Traumatic; Stress, Psychological

Topics: Acetamides; Adult; Female; Humans; Hypnotics and Sedatives; Receptors, Melatonin; Serotonin 5-HT2 Receptor Antagonists; Stress Disorders, Post-Traumatic

Treatment of survivors of political terror is an emerging and difficult field. Reports on posttraumatic stress disorder (PTSD) in political prisoners within the former Eastern Block countries is low and mostly restricted to German sources. During the totalitarian period administrative and clinical decisions often had to take into account political realities not found in other treatment environments. That practice might have lead to biased professional training, lack of experience extending into the post-communist era and leading to current underpresentation of PTSD. The authors present a case report of a Hungarian political prisoner with long history of PTSD who had a "carry over" diagnosis of paranoid schizophrenia even 15 years after the collapse of the communist regime. After decades of continuous administration of antipsychotic and antidepressive medications, either alone or in combination, Zeldox monotherapy has proven to be the most effective treatment for this patient.

Topics: Antipsychotic Agents; Communism; Diagnostic Errors; Humans; Hungary; Male; Middle Aged; Piperazines; Prisoners; Schizophrenia, Paranoid; Selective Serotonin Reuptake Inhibitors; Serotonin 5-HT2 Receptor Antagonists; Stress Disorders, Post-Traumatic; Thiazoles