Folic acid modulates cancer-associated micro RNAs and inflammatory mediators in neoplastic and non-neoplastic colonic cells in a different way.

SCOPE: Scientific evidence suggests that folic acid (FA) supplementation protects the healthy colonic mucosa from neoplastic transformation but may promote the progression of precancerous lesions. The underlying molecular mechanisms are not fully understood. Therefore, we explored, if high physiological FA doses provoke changes in (i) promoter-specific DNA methylation (ii) expression of cancer-associated micro RNAs (miRNAs) and (iii) inflammatory mediators in human neoplastic and non-neoplastic colonic cell lines. METHODS AND RESULTS: The malignant and the non-malignant colonic cell lines HT29 and HCEC were adapted to different near-physiological FA concentrations. Using DNA methylation and pathway specific PCR arrays, high-physiological FA concentrations revealed no relevant impact on promoter methylation but a number of differences between the cell lines in the expression of miRNAs and inflammatory mediators. In the HCEC cell line pro-inflammatory genes were repressed and the miRNA expression remained nearly unaffected. In contrast, in the HT29 cell line tumour-suppressive miRNAs were predominantly down-regulated and the expression of genes involved in chemotaxis and immunity were modulated. CONCLUSION: The different effects of high-physiological FA concentrations in malignant and non-malignant colonic cell lines regarding cancer-associated miRNAs and inflammatory mediators may contribute to the different effects of FA supplementation on colonic carcinogenesis.

[A two-faced vitamin : Folic acid - prevention or promotion of colon cancer?] / Ein Vitamin mit zwei Gesichtern : Folsäure ­ Prävention oder Promotion von Dickdarmkrebs?

In the late 1930s, it was discovered that liver and yeast extracts can be used to correct certain cases of megaloblastic anemia in pregnancy. The factor responsible for this was isolated from spinach leaves in the 1940s, and referred to as folate, a term derived from the Latin word folium for leaf. Folate is considered an essential nutrient for human beings. Folic acid, the synthetic form of the vitamin, is used in dietary supplements, medicines and fortified foods. Since the 1980s, it has been recommended that women who plan to become pregnant and pregnant women during the first trimester of pregnancy take folic acid supplements. This recommendation was based on studies that revealed that periconceptional folic acid supplementation can reduce the risk for neural tube defects (NTDs). Many countries later implemented folic acid fortification programs. The resulting population-wide increase of folic acid intakes led to significant reductions in NTD rates. However, a temporarily increased colorectal cancer incidence has been reported to coincide with the fortification programs in the USA and Canada. On the basis of currently available data from experimental and human studies it can be concluded that the association between folate/folic acid and cancer is rather complex: Folate intake in the range of the dietary reference intake (DRI) is associated with a reduced risk for cancer in healthy populations, whereas high intakes of folic acid might result in an increased risk for cancer incidence or progression in persons with precancerous lesions and under certain conditions. Since no adverse effects have been observed in association with the intake of dietary folate, research activities that aim at investigating cause and effect relationships focus on folic acid.

Reducing unwanted trauma memories by imaginal exposure or autobiographical memory elaboration: an analogue study of memory processes.

Unwanted memories of traumatic events are a core symptom of post-traumatic stress disorder. A range of interventions including imaginal exposure and elaboration of the trauma memory in its autobiographical context are effective in reducing such unwanted memories. This study explored whether priming for stimuli that occur in the context of trauma and evaluative conditioning may play a role in the therapeutic effects of these procedures. Healthy volunteers (N = 122) watched analogue traumatic and neutral picture stories. They were then randomly allocated to 20 min of either imaginal exposure, autobiographical memory elaboration, or a control condition designed to prevent further processing of the picture stories. A blurred picture identification task showed that neutral objects that preceded traumatic pictures in the stories were subsequently more readily identified than those that had preceded neutral stories, indicating enhanced priming. There was also an evaluative conditioning effect in that participants disliked neutral objects that had preceded traumatic pictures more. Autobiographical memory elaboration reduced the enhanced priming effect. Both interventions reduced the evaluative conditioning effect. Imaginal exposure and autobiographical memory elaboration both reduced the frequency of subsequent unwanted memories of the picture stories.

Enhanced priming for trauma-related words predicts posttraumatic stress disorder.

There is preliminary evidence that enhanced priming for trauma-related cues plays a role in posttraumatic stress disorder (PTSD). A prospective study of 119 motor vehicle accident survivors investigated whether priming for trauma-related stimuli predicts PTSD. Participants completed a modified word-stem completion test comprising accident-related, traffic-related, general threat, and neutral words at 2 weeks post-trauma. Priming for accident-related words predicted PTSD at 6 months follow-up, even when initial symptom levels of PTSD and depression and priming for other words were controlled. The results are in line with the hypothesis that enhanced priming for traumatic material contributes to the development of chronic PTSD.

Sex differences in heart rate responses to script-driven imagery soon after trauma and risk of posttraumatic stress disorder.

OBJECTIVE: To investigate in trauma survivors the predictive validity of heightened physiological responsivity to script-driven imagery for the development of posttraumatic stress disorder (PTSD) and to evaluate the interactive effect of survivors' sex. Physiological responses to idiosyncratic trauma reminders may be predictive of later PTSD. The majority of previous studies have been cross sectional and have produced mixed findings. Sex differences may contribute to this heterogeneity. METHODS: Heart rate (HR) and respiratory sinus arrhythmia were measured at 2 weeks post trauma in 158 assault survivors during baseline and as they listened to an idiosyncratic trauma script. At 6 months, 15.2% of male and 28.1% of female participants met the diagnostic criteria for PTSD. RESULTS: Generalized linear model and logistic regression analyses showed that HR response to script-driven imagery and sex interacted in predicting PTSD symptom severity at 6 months. Women had greater PTSD symptom severities overall. Female HR responders to script-driven imagery showed the highest PTSD symptom severities and were almost three times more likely to develop PTSD at 6 months compared with men and female nonresponders (odds ratio, 2.72; 95% confidence interval, 1.13-6.57). Respiratory sinus arrhythmia responder type did not predict PTSD (odds ratio, 0.64; 95% confidence interval, 0.30-1.33). CONCLUSION: Female trauma survivors who respond to trauma reminders with increased HR may be at particular risk of developing PTSD. Physiological reactivity to trauma cues may be a useful index for screening and prevention of PTSD.

Do all psychological treatments really work the same in posttraumatic stress disorder?

A recent meta-analysis by Benish, Imel, and Wampold (2008, Clinical Psychology Review, 28, 746-758) concluded that all bona fide treatments are equally effective in posttraumatic stress disorder (PTSD). In contrast, seven other meta-analyses or systematic reviews concluded that there is good evidence that trauma-focused psychological treatments (trauma-focused cognitive behavior therapy and eye movement desensitization and reprocessing) are effective in PTSD; but that treatments that do not focus on the patients' trauma memories or their meanings are either less effective or not yet sufficiently studied. International treatment guidelines therefore recommend trauma-focused psychological treatments as first-line treatments for PTSD. We examine possible reasons for the discrepant conclusions and argue that (1) the selection procedure of the available evidence used in Benish et al.'s (2008)meta-analysis introduces bias, and (2) the analysis and conclusions fail to take into account the need to demonstrate that treatments for PTSD are more effective than natural recovery. Furthermore, significant increases in effect sizes of trauma-focused cognitive behavior therapies over the past two decades contradict the conclusion that content of treatment does not matter. To advance understanding of the optimal treatment for PTSD, we recommend further research into the active mechanisms of therapeutic change, including treatment elements commonly considered to be non-specific. We also recommend transparency in reporting exclusions in meta-analyses and suggest that bona fide treatments should be defined on empirical and theoretical grounds rather than by judgments of the investigators' intent.

Imagery special issue: intrusive images and memories of earlier adverse events in patients with obsessive compulsive disorder.

Mental imagery is increasingly considered to be an important feature in anxiety disorders. The aim of this study was to investigate the prevalence and characteristics of mental images in obsessive compulsive disorder (OCD) and their possible association with earlier adverse events. A consecutive sample of 37 patients with OCD admitted to a specialist unit was interviewed using a semi-structured interview. Thirty (81%) patients with OCD reported mental images. Most images were either memories of earlier adverse events (n=10 or 34%) or were associated with them (n=13 or 45%). Patients with mental images had more obsessive compulsive symptoms, responsibility beliefs and anxiety than those without. Previous research has shown that patients with OCD and comorbid posttraumatic stress disorder might not benefit as much from standard behavioural treatment as those without. Consequently, additional therapeutic interventions such as imaginal reliving and restructuring of meaning or imagery modification of traumatic memories might be helpful in OCD patients with mental images that are linked to earlier adverse events.

Overgeneral memory extends to pictorial retrieval cues and correlates with cognitive features in posttraumatic stress disorder.

Individuals with posttraumatic stress disorder (PTSD) show overgeneral memory (OGM) when retrieving autobiographical memories to word cues. We investigated whether OGM extends to picture cues and whether it is related to PTSD symptoms and cognitions. Trauma survivors with (n = 29) and without (n = 26) PTSD completed the standard Autobiographical Memory Test (AMT) and a novel picture version. Compared to the no-PTSD group, the PTSD group showed OGM in both test versions. Pictures facilitated specific memory retrieval, but this effect was no longer significant when verbal intelligence or depressive symptoms were controlled. OGM correlated with PTSD symptoms and perceived self-change; with intrusive memories, their perceived "nowness," responses to intrusions (thought suppression, rumination, dissociation), and negative interpretations of symptoms.

Cognitive therapy versus exposure and applied relaxation in social phobia: A randomized controlled trial.

A new cognitive therapy (CT) program was compared with an established behavioral treatment. Sixty-two patients meeting Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994) criteria for social phobia were randomly assigned to CT, exposure plus applied relaxation (EXP = AR), or wait-list (WAIT). CT and EXP = AR were superior to WAIT on all measures. On measures of social phobia, CT led to greater improvement than did EXP = AR. Percentages of patients who no longer met diagnostic criteria for social phobia at posttreatment-wait were as follows: 84% in CT, 42% in EXP = AR, and 0% in WAIT. At the 1-year follow-up, differences in outcome persisted. In addition, patients in EXP = AR were more likely to have sought additional treatment. Therapist effects were small and nonsignificant. CT appears to be superior to EXP = AR in the treatment of social phobia.