Epigenetics and memory: causes, consequences and treatments for post-traumatic stress disorder and addiction.

Understanding the interaction between fear and reward at the circuit and molecular levels has implications for basic scientific approaches to memory and for understanding the etiology of psychiatric disorders. Both stress and exposure to drugs of abuse induce epigenetic changes that result in persistent behavioral changes, some of which may contribute to the formation of a drug addiction or a stress-related psychiatric disorder. Converging evidence suggests that similar behavioral, neurobiological and molecular mechanisms control the extinction of learned fear and drug-seeking responses. This may, in part, account for the fact that individuals with post-traumatic stress disorder have a significantly elevated risk of developing a substance use disorder and have high rates of relapse to drugs of abuse, even after long periods of abstinence. At the behavioral level, a major challenge in treatments is that extinguished behavior is often not persistent, returning with changes in context, the passage of time or exposure to mild stressors. A common goal of treatments is therefore to weaken the ability of stressors to induce relapse. With the discovery of epigenetic mechanisms that create persistent molecular signals, recent work on extinction has focused on how modulating these epigenetic targets can create lasting extinction of fear or drug-seeking behavior. Here, we review recent evidence pointing to common behavioral, systems and epigenetic mechanisms in the regulation of fear and drug seeking. We suggest that targeting these mechanisms in combination with behavioral therapy may promote treatment and weaken stress-induced relapse.

A comparison of driving in older subjects with and without age-related macular degeneration.

OBJECTIVE: To determine the effects of age and central vision loss on driving skills. METHODS: Ten subjects with age-related macular degeneration and average binocular visual acuity of 20/70, and 11 age-similar subjects with normal vision, were examined with a battery of cognitive and visual tests, an interactive driving simulator, and an on-road driving test. Data were collected on the frequency of real-world accidents and convictions for traffic violations. RESULTS: There were no significant differences between the two groups on any of the cognitive tests. The age-related macular degeneration group demonstrated poorer performance on the driving simulator, including delayed braking response times to stop signs, slower speeds, and more of both lane boundary crossings and simulator accidents. The age-related macular degeneration group also demonstrated poorer overall on-road test performance, including having significantly more points deducted for driving too slowly and for not maintaining proper lane position. However, these effects on the simulator and the on-road test did not translate into an increased risk of real-world accidents for the age-related macular degeneration group. Significantly more control subjects than patients with age-related macular degeneration were involved in self-reported accidents, and significantly more control subjects had state convictions for traffic violations. There was evidence of compensation in the age-related macular degeneration group in four major areas: (1) not driving in unfamiliar areas; (2) traveling at slow speeds; (3) self-restricting their nighttime driving, and (4) taking fewer risks while driving (eg, not changing lanes). There was also evidence of compensation in the older control group. CONCLUSIONS: Vision, simulator, and on-road test variables combined with subjective risk taking predicted self-reported real-world accidents in a logistic regression analysis. However, risk taking, rather than simulator or road-test performance, was the most significant predictor for both patients with age-related macular degeneration and the control group.

[Psycho-emotional distress and gastroesophageal reflux syndrome]. / Distress psico-emozionali e sindrome da reflusso gastroesofageo.

61 patients with symptoms suggestive for gastro-esophageal reflux (GER) disease, with or without endoscopic evidence of esophagitis, were studied in order to recognize any neurotic traits connected to GERD and its esophageal motility disorders. The results were compared with those from a group of patients without digestive diseases as well as those from a control group of the same age and status. Psychological assessment was made by using the Middlesex Hospital Questionnaire and esophageal motility pattern was analyzed with a low-compliance manometric system. Patients with gastro-esophageal reflux (GER), irrespectively or not from esophagitis, showed, after such a psychological assessment, neurotic traits more pronounced than control subjects and patients without digestive disease. In GER patients, it was observed a close relationship between some psychological traits and a few esophageal manometric variable. In the two groups of GER patients, with and without esophagitis, it was not found any significant difference in scores referring to the evaluated psychological traits apart from symptoms somatization, prevailing in GER patients without esophagitis. These results support the pathogenetic role of psychological distresses in the genesis of GER, even if other factors may be necessary to the development of organic inflammatory lesions such as esophagitis.

[Effects of intravenous administration of clarithromycin on plasma levels of gastrin and group I pepsinogen]. / Effetti della somministrazione venosa di claritromicina sui livelli plasmatici di gastrina e pepsinogeno del gruppo I.

Erythromycin and some of its derivatives have prokinetic gastrointestinal properties. In addition, erythromycin has been shown to stimulate isolated chief cells of the gastric mucosa, and to activate pepsin secretion. The above study was aimed at ascertaining in a group of dyspeptic patients whether clarithromycin, a structural analogue of erythromycin, is apt to modify certain functional parameters of gastric secretion, above all the patterns of gastrin and PG-I secretion. A 20-minute intravenous clarithromycin infusion (1.5 mg/kg) in fasting subjects has brought about a significant reduction (at 20 and 45 minutes from the start of infusion) of circulating gastrin (about 23%) and, after a meal, a 69% increase. No change of plasma PG-I level was observed either after placebo or after the active substance. These findings suggest that in vivo and at the doses used in our experiment clarithromycin has no influence on plasma PG-I release and is apt to modify the fasting and postprandial gastrin releasing pattern.

[The esophageal motor pattern and the acid exposure of the distal esophagus in patients with gastroesophageal reflux]. / Pattern motorio esofageo ed esposizione acida dell'esofago distale in pazienti con malattia da reflusso gastro-esofageo.

Low-compliance standard manometry and 24-hour ambulatory pH monitoring were performed in 42 patients with typical gastro-esophageal reflux (GER) symptoms in order to assess correlations between esophageal motility pattern and pH profile. Our results show: 1) 36% of GER patients had a normal esophageal acid exposure; 2) pH profile and manometric pattern did not differ in patients with mild esophagitis from those without esophagitis; 3) low esophageal sphincter pressure in GER patients was significantly lower than in control subjects, irrespective of acid exposure; 4) the main motility disorders in the distal esophagus of reflux patients was the increased simultaneous wave rate which seemed to affect both recumbent esophageal clearance and reflux time.