he pathological fear of interaction with men

#He pathological fear of interaction with men series

Given the recent findings suggesting that the facilitative effects of other cognitive enhancers such as D-cycloserine ( 33) and yohimbine ( 34) may depend on the post-training clinical status of the patient, we hypothesized that methylene blue would enhance fear extinction retention at follow-up for participants who achieved low levels of fear at post-training. Moreover, the rate of cytochrome c oxidation in brain homogenates of these animals showed a 38% increase in absolute brain metabolic activity relative to controls administered saline, whereas cytochrome oxidase histochemistry revealed the largest effect on the prefrontal cortex ( 22), a brain region clearly implicated in fear extinction ( 30- 32).īased on these preclinical studies, we sought to test whether post-extinction methylene blue administration enhances the retention of pathological fear attenuation in phobic individuals receiving extinction training. Gonzalez-Lima and colleagues ( 22, 29) found that memory retention of extinction after Pavlovian fear conditioning could be improved with the administration of 4 mg/kg methylene blue post-extinction. Post-training administration of low methylene blue doses in rodents has been shown to improve memory retention in a variety of tasks, including inhibitory avoidance ( 23, 24), spatial memory ( 24- 27), discrimination learning ( 28), and most relevant to the present study, retention of conditioned fear extinction ( 22, 29). Hence, by acting as a mitochondrial electron cycler and antioxidant, low-dose methylene blue increases cellular energy production and support enhanced memory consolidation in key brain regions associated with memory processing ( 19). Although methylene blue has the potential to enter any nerve cell, it preferentially accumulates in neurons with higher energy demand, such as those involved in memory consolidation after extinction training ( 22). By enhancing cytochrome oxidase activity, methylene blue increases oxygen consumption and amount of ATP available in neurons during memory consolidation.

Preclinical research with rodents has shown that at low doses, methylene blue is a metabolic and cognitive enhancer that improves brain oxygen consumption, brain glucose uptake, cerebral blood flow, fMRI responses and memory consolidation by induction of cytochrome oxidase, the respiratory enzyme found within nerve cells ( 19- 21). Methylene blue is a diaminophenothiazine drug that at low doses (0.5 - 4 mg/kg) has neurometabolic-enhancing properties ( 19). Available in every emergency room as an antidote against metabolic poisons, methylene blue has been used safely for well over a hundred years ( 18). Overall, findings have been mixed with some showing strong augmentation effects ( 7- 10), others showing weak ( 11- 13) or negligible effects ( 14- 16) and one study showing detrimental effects ( 17).Īnother promising pharmacological agent that has received significant support in preclinical studies is methylene blue.

#He pathological fear of interaction with men series

Based on early preclinical data demonstrating that D-cycloserine enhances fear extinction in rats ( 5), a series of randomized clinical trials have examined the clinical efficacy of exposure therapy with D-cycloserine augmentation across a range of anxiety disorders. The most widely studied of these is D-cycloserine, an N-methyl-D-aspartate receptor co-agonist. Significant advances in cognitive and behavioral neuroscience have led to a better understanding of fear extinction and have ushered in a new era of “translational” research focusing on the integration of findings from these basic science disciplines to improve extinction-based therapies for anxiety disorders ( 3, 4).Ī recent development in exposure therapy research is the use of memory enhancing pharmacological agents to boost fear extinction during exposure therapy. Over the past four decades, research on exposure therapy has shifted from demonstrating therapeutic efficacy to the study of change mechanisms and augmentation strategies to improve short-term efficacy and reduce return of fear ( 1) ( 2).