Testing the Paleolithic-human-warfare hypothesis of blood-injectiion phobia in the Balitmore ECA Follow-up Study-Towards a more etiologically-based conceptualization for DSM-V

Objective: The research agenda for the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) has emphasized the need for a more etiologically-based classification system, especially for stress-induced and fear-circuitry disorders. Testable hypotheses based on threats to survival during particular segments of the human era of evolutionary adaptedness (EEA) may be useful in developing a brain-evolution-based classification for the wide spectrum of disorders ranging from disorders which are mostly overconsolidationally such as PTSD, to fear-circuitry disorders which are mostly innate such as specific phobias. The recently presented Paleolithic-human-warfare hypothesis posits that blood–injection phobia can be traced to a “survival (fitness) enhancing” trait, which evolved in some females of reproductive-age during the millennia of intergroup warfare in the Paleolithic EEA. The study presented here tests the key a priori prediction of this hypothesis—that current blood–injection phobia will have higher prevalence in reproductive-age women than in post-menopausal women. Method: The Diagnostic Interview Schedule (version III-R) , which included a section on blood and injection phobia, was administered to 1920 subjects in the Baltimore ECA Follow-up Study. Results: Data on BII phobia was available on 1724 subjects (1078 women and 646 males) . The prevalence of current blood– injection phobia was 3.3% in women aged 27–49 and 1.1% in women over age 50 (OR 3.05, 95% CI 1.20–7.73) . [The corresponding figures for males were 0.8% and 0.7% (OR 1.19, 95% CI 0.20–7.14)] . Conclusions: This epidemiological study provides one source of support for the Paleolithic-human-warfare (Paleolithic-threat) hypothesis regarding the evolutionary (distal) etiology of bloodletting-related phobia, and may contribute to a more brain- evolution-based re-conceptualization and classification of this fear circuitry-related trait for the DSM-V. In addition, the finding reported here may also stimulate new research directions on more proximal mechanisms which can lead to the development of evidence-based psychopharmacological preventive interventions for this common and sometimes disabling fear-circuitry disorder

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

The prenatal origins of cancer

The concept that some childhood malignancies arise from postnatally persistent embryonal cells has a long history. Recent research has strengthened the links between driver mutations and embryonal and early postnatal development. This evidence, coupled with much greater detail on the cell of origin and the initial steps in embryonal cancer initiation, has identified important therapeutic targets and provided renewed interest in strategies for the early detection and prevention of childhood cancer. © 2014 Macmillan Publishers Limited. All rights reserved