Pharmacological treatments that facilitate extinction of fear: Relevance to psychotherapy

A great deal is now known about the mechanisms of conditioned fear acquisition and expression. More recently, the mechanisms of inhibition of conditioned fear have become the subject of intensive study. The major model system for the study of fear inhibition in the laboratory is extinction, in which a previously fear conditioned organism is exposed repeatedly to the fear-eliciting cue in the absence of any aversive event and the fear conditioned response declines. It is well established that extinction is a form of new learning as opposed to forgetting or “unlearning” of conditioned fear, and it is hypothesized that extinction develops when sensory pathways conveying sensory information to the amygdala come to engage GABAergic interneurons through forms of experience-dependent plasticity such as long-term potentiation. Several laboratories currently are investigating methods of facilitating fear extinction in animals with the hope that such treatments might ultimately prove to be useful in facilitating exposure-based therapy for anxiety disorders in clinical populations. This review discusses the advances that have been made in this field and presents the findings of the first major clinical study to examine the therapeutic utility of a drug that facilitates extinction in animals. It is concluded that extinction is an excellent model system for the study of fear inhibition and an indispensable tool for the screening of putative pharmacotherapies for clinical use.     

A Qualitative Inquiry About Pruno,an Illicit Alcoholic Beverage Linked to Botulism Outbreaks in United States Prisons

Objectives. Since 2011, 3 outbreaks of botulism in US prisons have been attributed to pruno, which is an alcoholic beverage made by inmates. Following 1 outbreak, we conducted a qualitative inquiry to understand pruno brewing and its social context to inform outbreak prevention measures.Methods. We interviewed staff, inmates, and parolees from 1 prison about pruno production methods, the social aspects of pruno, and strategies for communicating the association between botulism and pruno.Results. Twenty-seven inmates and parolees and 13 staff completed interviews. Pruno is fermented from water, fruit, sugar, and miscellaneous ingredients. Knowledge of pruno making was widespread among inmates; staff were familiar with only the most common ingredients and supplies inmates described. Staff and inmates described inconsistent consequences for pruno possession and suggested using graphic health messages from organizations external to the prison to communicate the risk of botulism from pruno.Conclusions. Pruno making was frequent in this prison. Improved staff recognition of pruno ingredients and supplies might improve detection of brewing activities in this and other prisons. Consistent consequences and clear messages about the association between pruno and botulism might prevent outbreaks.Botulism is a rare but serious illness that can lead to respiratory failure and death. Botulism patients may initially present with blurred or double vision, drooping eyelids, slurred speech, and difficulty swallowing before developing more severe signs and symptoms, such as paralysis and difficulty breathing. In the United States, an average of 145 confirmed botulism cases are reported each year, of which approximately 15% are attributable to foodborne botulism.1 Foodborne botulism is caused by ingestion of botulinum toxin, a bacterial toxin that is produced under the following rarely attained conditions: an anaerobic environment with warm temperatures and low acid, salt, and sugar concentrations.2 Alaska Native foods and home-canned vegetables are the food items most commonly associated with foodborne botulism3,4; however, in the past decade, 5 foodborne botulism outbreaks have been attributed to pruno, an illicit alcoholic beverage made in prisons.5 Pruno was initially recognized as a botulism vehicle after it was implicated in 2 outbreaks in California in 2004 and 2005; these outbreaks resulted in confirmed botulism in 5 inmates, 3 of whom were critically ill and mechanically ventilated.6 No additional outbreaks were reported until 2011, when 8 maximum security inmates in Utah developed botulism after drinking pruno. Three were mechanically ventilated, and most reported persistent symptoms, such as weakness, 11 months after the outbreak.7 The following year, 12 Arizona inmates were sickened in 2 outbreaks of botulism associated with pruno consumption; 8 were mechanically ventilated.5 In all 5 outbreaks, pruno was made with potatoes,5 an uncommon pruno ingredient according to online sources, and a food historically associated with botulism.8,9 Because of these outbreaks, pruno-related botulism accounted for 40% and 48% of foodborne botulism cases in the United States in 2011 and 2012, respectively (Centers for Disease Control and Prevention, unpublished data).Internet sources indicate that pruno is common in US prisons.10–12 Although recent trends suggest future pruno-related botulism outbreaks are likely to occur,5,7 there is a dearth of information about how pruno is made and distributed in prisons, and the social and entrepreneurial aspects of its production and use. To address these gaps and inform botulism outbreak prevention measures, 4 months after the Utah outbreak, we conducted a qualitative inquiry in the affected prison to better understand the brewing process, social context of pruno, and communication strategies for informing inmates about the risk of botulism from pruno.