Chronic methamphetamine abuse commonly leads to psychosis, with positive and cognitive symptoms that are similar to those of schizophrenia. Methamphetamine induced psychosis (MAP) can persist and diagnoses of MAP often change to a diagnosis of schizophrenia over time. Studies in schizophrenia have found much evidence of cortical GABAergic dysfunction. Methamphetamine psychosis is a well studied model for schizophrenia, however there is little research on the effects of methamphetamine on cortical GABAergic function in the model, and the neurobiology of MAP is unknown. This paper reviews the effects of methamphetamine on dopaminergic pathways, with focus on its ability to increase glutamate release in the cortex. Excess cortical glutamate would likely damage GABAergic interneurons, and evidence of this disturbance as a result of methamphetamine treatment will be discussed. We propose that cortical GABAergic interneurons are particularly vulnerable to glutamate overflow as a result of subcellular location of NMDA receptors on interneurons in the cortex. Damage to cortical GABAergic function would lead to dysregulation of cortical signals, resulting in psychosis, and further support MAP as a model for schizophrenia.

Most epidemiologic studies on folate intake suggest that folate may be protective against colorectal cancer, but the results on circulating (plasma or serum) folate are mostly inconclusive. We conducted a meta-analysis of case-control studies nested within prospective studies on circulating folate and colorectal cancer risk by using flexible meta-regression models to test the linear and nonlinear dose-response relationships. A total of 8 publications (10 cohorts, representing 3,477 cases and 7,039 controls) were included in the meta-analysis. The linear and nonlinear models corresponded to relative risks of 0.96 (95% confidence interval (CI): 0.91, 1.02) and 0.99 (95% CI: 0.96, 1.02), respectively, per 10 nmol/L of circulating folate in contrast to the reference value. The pooled relative risks when comparing the highest with the lowest category were 0.80 (95% CI: 0.61, 0.99) for radioimmunoassay and 1.03 (95% CI: 0.83, 1.22) for microbiological assay. Overall, our analyses suggest a null association between circulating folate and colorectal cancer risk. The stronger association for the radioimmunoassay-based studies could reflect differences in cohorts and study designs rather than assay performance. Further investigations need to integrate more accurate measurements and flexible modeling to explore the effects of folate in the presence of genetic, lifestyle, dietary, and hormone-related factors.

The recent release of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) by the American Psychiatric Association has led to much debate. For this forum article, we asked BMC Medicine Editorial Board members who are experts in the field of psychiatry to discuss their personal views on how the changes in DSM-5 might affect clinical practice in their specific areas of psychiatric medicine. This article discusses the influence the DSM-5 may have on the diagnosis and treatment of autism, trauma-related and stressor-related disorders, obsessive-compulsive and related disorders, mood disorders (including major depression and bipolar disorders), and schizophrenia spectrum disorders.

Across therapeutic areas, the Norwegian research investments appeared aligned with the Norwegian disease burden. The correlation between the Norwegian research investments and the global disease burden was much lower.

Qualitative research may provide useful insights for the design of interventions of this nature related to social inclusion randomised control trials with its focus on adherence.

The birth prevalence of CHD declined from around 2005. Specifically, the prevalence of severe CHD was reduced by 3.4% per year from 2004 through 2009.

Although a great deal of information about the neurobiology of panic disorder is now available, there is a need for an updated etiological model integrating recent findings on the neurobiology of the arousal system and its relationship with higher cortical functions in panic disorder. The current mini-review presents psychophysiological, molecular biological/genetic and functional neuroimaging evidence for dysfunction in major arousal systems of the brain. Such dysfunction may influence the development of panic disorder by precipitating autonomic bodily symptoms and at the same time increasing vigilance to these sensations by modulating cortical attentional networks. A multilevel model of arousal, attention and anxiety-including the norepinephrine, orexin, neuropeptide S and caffeine-related adenosine systems-may be useful in integrating a range of data available on the pathogenesis of panic disorder.

Background Well-conducted treatment trials and data on predictors of treatment response are both lacking for ADWA, despite the high prevalence of the condition. While benzodiazepines are frequently prescribed for anxiety disorders, etifoxine is also an effective agent not associated with dependence. A randomized controlled trial of etifoxine versus alprazolam for ADWA was undertaken, aiming at comparing efficacy and safety of the two treatments, and investigating predictors of the clinical response. Methods Two hundred and two adult outpatients with ADWA were enrolled at primary care settings sites in South Africa. Patients were followed for 4 weeks of treatment, and for an additional week after treatment discontinuation. The primary outcome measure was the Hamilton Anxiety Rating Scale (HAM-A) and was assessed by using a non-inferiority analysis. Secondary outcomes included the Sheehan Disability Scale (SDS) and the Clinical Global Impressions-Change Scale (CGI-C). Predictors of response were investigated with a multivariate logistic regression. Results Both etifoxine and alprazolam dramatically decreased the HAM-A score at 4 weeks. The difference between treatment groups in HAM-A was of 1.78 [90% CI; 0.23, 3.33] in favor of alprazolam. The two treatments were equally efficacious in patients with more severe anxiety symptoms at baseline. Between week 4 and week 5, after treatment discontinuation, HAM-A scores continued to improve in the etifoxine group, but increased in the alprazolam group ( P = 0.019); no difference was found between the two groups regarding the secondary outcomes. No significant predictors of treatment response were found. Patients treated with alprazolam experienced more treatment-related adverse events, mostly of central nervous origin, and especially after medication discontinuation. Conclusion This trial confirms the efficacy and safety of etifoxine in the management of ADWA.

We did not observe statistical evidence for substantial differences between cases and controls for any of the measured analytes. Analyses specifically targeting B-vitamins also did not reveal differences between cases and controls.

Lower bone mineral density (BMD) in smokers may be attributable to lower body weight or fat mass, rather than to a direct effect of smoking. We analyzed the effects of smoking exposure, assessed by plasma cotinine, and body fat on BMD and the risk of subsequent hip fracture. In the community-based Hordaland Health Study (HUSK), 3003 participants 46-49 years and 2091 subjects 71-74 years were included. Cotinine was measured in plasma and information on health behaviors was obtained from self-administered questionnaires. BMD and total body soft tissue composition were measured by dual X-ray absorptiometry. Information on hip fracture was obtained from computerized records containing discharge diagnoses for hospitalizations between baseline examinations 1997-2000 through December 31st, 2009. In the whole cohort, moderate and heavy smokers had stronger positive associations between fat mass and BMD compared to never smokers (differences in regression coefficient (95% CI) per % change in fat mass = 1.38 (0.24, 2.52) and 1.29 (0.17, 2.4), respectively). In moderate and heavy smokers there was a nonlinear association between BMD and fat mass with a stronger positive association at low compared to high levels of fat mass (Davies segmented test, p<0.001). In elderly women and men, heavy smokers had an increased risk of hip fracture compared to never smokers (hazard ratio = 3.31, 95% CI: 2.05, 5.35; p<0.001). In heavy smokers there was a tendency of a lower risk of hip fracture with higher percentage of fat mass. The deleterious effect of smoking on bone health is stronger in lean smokers than in smokers with high fat mass.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: Primary Objective To determine whether antidepressants are clinically efficacious in the treatment of depression in adults infected with HIV. Secondary Objectives To determine which anti‐depressant class is most efficacious for the treatment of depression in adults infected with HIV. To determine if the side‐effect profile of antidepressant therapy is tolerable for adults infected with HIV. To determine if antidepressant therapy is acceptable to adults infected with HIV.

Being born with low birthweight is associated with smoking in adulthood. Associations of adult smoking with partners' birthweight and mothers' smoking-related causes of death suggest a shared smoking environment, and may account for some of the established association between birthweight and later cardiovascular disease.

Our results support the notion that childhood maltreatment is associated with impaired empathy, and suggest that such impairment may differ depending on the level of maltreatment: moderate maltreatment was associated with emotional blunting and impaired cognitive empathy, whereas severe maltreatment was associated with emotional over-arousal and diminished cognitive insight.