Predicting suicide attempts in young adults with histories of childhood abuse

BACKGROUND: Although childhood abuse is an important correlate of suicidality, not all individuals who were abused as children attempt suicide. AIMS: To identify correlates and moderators of suicide attempts in adults reporting childhood physical abuse, contact sexual abuse, or both. METHOD: A French-Canadian, school-based cohort (n=1684) was prospectively followed. RESULTS: The identity of the abuser moderated the relationship of abuse frequency and suicide attempts, with individuals abused by their immediate family being at highest risk. Although paternal education exhibited negative associations (OR=0.71, 95% CI 0.58-0.88), several externalising phenotypes had positive associations with suicide attempts: disruptive disorders (OR=3.10, 95% CI 1.05-9.15), conduct problems (OR=1.09, 95% CI 1.01-1.19) and childhood aggression (OR=1.41, 95% CI 1.08-1.83). CONCLUSIONS: Characteristics of the abuser and abusive acts may be important additional indicators of risk for suicide attempts. Future research needs to employ developmental approaches to examine the extent and mechanisms by which childhood abuse contributes to the shared variance of suicidality, maladaptive traits and psychopathology.     

Endogenous conversion of omega-6 into omega-3 fatty acids improves neuropathology in an animal model of Alzheimer's disease

Dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFA) reduces amyloid-β (Aβ) and tau pathology and improves cognitive performance in animal models of Alzheimer's disease (AD). To exclude confounding variables associated with the diet, we crossed 3 × Tg-AD mice (modeling AD neuropathology) with transgenic Fat-1 mice that express the fat-1 gene encoding a PUFA desaturase, which endogenously produces n-3 PUFA from n-6 PUFA. The expression of fat-1 shifted the n-3:n-6 PUFA ratio upward in the brain (+11%, p < 0.001), including docosahexaenoic acid (DHA; +5%, p < 0.001) in 20 month-old mice. The expression of fat-1 decreased the levels of soluble Aβ?? (-41%, p < 0.01) at 20 months without reducing the level of insoluble forms of Aβ?? and Aβ?? in the brain of 3 × Tg-AD mice. The 3 × Tg-AD/Fat-1 mice exhibited lower cortical levels of both soluble (-25%, p < 0.05) and insoluble phosphorylated tau (-55%, p < 0.05) compared to 3 × Tg-AD mice, but only in 20 month-old animals. Whereas a decrease of calcium/calmodulin-dependent protein kinase II was observed in 3 × Tg-AD/Fat-1 mice (-039%, p < 0.05), altered tau phosphorylation could not be related to changes in glycogen synthase kinase 3β, cyclin-dependent kinase 5, or protein phosphatase type 2A enzymatic activity. In addition, the expression of the fat-1 transgene prevented the increase of glial fibrillary acidic protein (-37%, p < 0.01) observed in 20 month-old 3 × Tg-AD mice. In conclusion, the expression of fat-1 in 3 × Tg-AD mice increases brain DHA and induces biomarker changes that are consistent with a beneficial effect against an AD-like neuropathology.     

Grammar predicts procedural learning and consolidation deficits in children with Specific Language Impairment

The Procedural Deficit Hypothesis (PDH) posits that Specific Language Impairment (SLI) can be largely explained by abnormalities of brain structures that subserve procedural memory. The PDH predicts impairments of procedural memory itself, and that such impairments underlie the grammatical deficits observed in the disorder. Previous studies have indeed reported procedural learning impairments in SLI, and have found that these are associated with grammatical difficulties. The present study extends this research by examining consolidation and longer-term procedural sequence learning in children with SLI. The Alternating Serial Reaction Time (ASRT) task was given to children with SLI and typically developing (TD) children in an initial learning session and an average of three days later to test for consolidation and longer-term learning. Although both groups showed evidence of initial sequence learning, only the TD children showed clear signs of consolidation, even though the two groups did not differ in longer-term learning. When the children were re-categorized on the basis of grammar deficits rather than broader language deficits, a clearer pattern emerged. Whereas both the grammar impaired and normal grammar groups showed evidence of initial sequence learning, only those with normal grammar showed consolidation and longer-term learning. Indeed, the grammar-impaired group appeared to lose any sequence knowledge gained during the initial testing session. These findings held even when controlling for vocabulary or a broad non-grammatical language measure, neither of which were associated with procedural memory. When grammar was examined as a continuous variable over all children, the same relationships between procedural memory and grammar, but not vocabulary or the broader language measure, were observed. Overall, the findings support and further specify the PDH. They suggest that consolidation and longer-term procedural learning are impaired in SLI, but that these impairments are specifically tied to the grammatical deficits in the disorder. The possibility that consolidation and longer-term learning are problematic in the disorder suggests a locus of potential study for therapeutic approaches. In sum, this study clarifies our understanding of the underlying deficits in SLI, and suggests avenues for further research.     

No association between resting metabolic rate or respiratory exchange ratio and subsequent changes in body mass and fatness: 5-1/2 year follow-up of the Québec family study

OBJECTIVE: To investigate the relationships between resting metabolic rate (RMR) and respiratory exchange ratio (RER) and subsequent changes in body size and fatness. DESIGN: Prospective longitudinal observational study. PARTICIPANTS: A sample of 147 participants (76 males, 71 females) 18-68 y of age were followed for approximately 5-1/2 y. MEASURES: At baseline, post-absorptive RMR and RER were determined by indirect calorimetry and adjusted for the effects of age, body mass and subcutaneous fatness using regression procedures. Indicators of body size and fatness included body mass, waist circumference, and the sum of six skinfolds. Changes in these indicators (delta scores) were adjusted for age and length of the follow-up period using regression. RESULTS: Correlations between baseline RMR, RER and subsequent changes in the indicators of body fatness were uniformly low and not significant (range -0.05-0.16). Further, Cox proportional hazards regression analyses indicated that neither RMR nor RER were significant predictors of gains in body mass, waist circumference, or the sum of six skinfolds. CONCLUSIONS: There is no association between RMR or RER and changes in indicators of body size and fatness over 5(1/2) y of follow-up in this sample. European Journal of Clinical Nutrition (2000) 54, 610-614     

Electroretinographic oscillatory potentials are reduced in adenylyl cyclase type I deficient mice

Electroretinography (ERG) of adult Adcy1(brl) mutant mice, which are deficient in adenylyl cyclase type 1 (AC1) activity, revealed decreased amplitude of the oscillatory potentials (OP) and of the primary rising phase of the b-wave intensity-response function in scotopic conditions. These abnormalities were less discernable in 3-6 week old mutants. No abnormalities were detected in the ERG signal obtained in photopic conditions or in the dark adaptation dynamics. The mutants displayed no histologic evidence of retinal degeneration. Retinal output, as measured by visual evoked potentials, was not different from heterozygous control mice. AC1-dependent pathways contribute to the generation of the retinal response to light. They may be necessary for the maintenance of the neural generators of the ERG OP.     

Cell therapies for inherited myopathies

PURPOSE OF REVIEW: Cell therapies for inherited myopathies are based on the implantation of normal or genetically corrected myogenic cells into the body. This review summarizes the recent progress in this field, systematized according to the factors important for success. RECENT FINDINGS: In the choice of donor cells, myoblasts derived from satellite cells remain the best choice.Some studies on the population of muscle-derived stem cells in mice suggested that these cells may have some advantages over myoblasts; however, no results supporting this advantage have been presented in a primate model. Recent studies on bone marrow transplantation as a systemic source of myogenic precursors for the treatment of myopathies were disappointing. Concerning donor cell delivery, intramuscular myoblast injection remains the only way that can significantly introduce exogenous myogenic cells into the muscles. A recent study in primates showed some parameters of myoblast injection that could be useful in the human. Progress was made in mice to understand the factors that could favor the migration of the donor myoblasts in the host muscles. Concerning donor cell survival, analysis of immune cell infiltration dynamics allowed a better understanding of the factors implicated in early donor cell death. Progress was made on the control of acute rejection for myoblast transplantation in primates. So far, few mouse experiments have advanced the field of tolerance induction toward myogenic cells. SUMMARY: Myoblast transplantation (intramuscular injection of satellite cell-derived myoblasts) currently remains the only cell-based therapy that has produced promising results in the context of a preclinical model such as the nonhuman primate.