Parental Depression, Maternal Antidepressant Use During Pregnancy, and Risk of Autism Spectrum Disorders: Population Based Case-Control Study.

Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: population based case-control study.

BMJ. 2013; 346: f2059
Rai D, Lee BK, Dalman C, Golding J, Lewis G, Magnusson C

To study the association between parental depression and maternal antidepressant use during pregnancy with autism spectrum disorders in offspring.Population based nested case-control study.Stockholm County, Sweden, 2001-07.4429 cases of autism spectrum disorder (1828 with and 2601 without intellectual disability) and 43?277 age and sex matched controls in the full sample (1679 cases of autism spectrum disorder and 16?845 controls with data on maternal antidepressant use nested within a cohort (n=589?114) of young people aged 0-17 years.A diagnosis of autism spectrum disorder, with or without intellectual disability. EXPOSURES: Parental depression and other characteristics prospectively recorded in administrative registers before the birth of the child. Maternal antidepressant use, recorded at the first antenatal interview, was available for children born from 1995 onwards.A history of maternal (adjusted odds ratio 1.49, 95% confidence interval 1.08 to 2.08) but not paternal depression was associated with an increased risk of autism spectrum disorders in offspring. In the subsample with available data on drugs, this association was confined to women reporting antidepressant use during pregnancy (3.34, 1.50 to 7.47, P=0.003), irrespective of whether selective serotonin reuptake inhibitors (SSRIs) or non-selective monoamine reuptake inhibitors were reported. All associations were higher in cases of autism without intellectual disability, there being no evidence of an increased risk of autism with intellectual disability. Assuming an unconfounded, causal association, antidepressant use during pregnancy explained 0.6% of the cases of autism spectrum disorder.In utero exposure to both SSRIs and non-selective monoamine reuptake inhibitors (tricyclic antidepressants) was associated with an increased risk of autism spectrum disorders, particularly without intellectual disability. Whether this association is causal or reflects the risk of autism with severe depression during pregnancy requires further research. However, assuming causality, antidepressant use during pregnancy is unlikely to have contributed significantly towards the dramatic increase in observed prevalence of autism spectrum disorders as it explained less than 1% of cases. HubMed – addiction


Socioeconomic Deprivation and Hospital Length of Stay: A New Approach Using Area-based Socioeconomic Indicators in Multilevel Models.

Med Care. 2013 Apr 17;
Coevoet V, Fresson J, Vieux R, Jay N

BACKGROUND:: Socioeconomic deprivation is not easily measurable in hospital information systems. However, its identification is essential, as it is associated with morbidity and hospital length of stay (LOS). We aimed at studying the feasibility of using routinely recorded individual and area-based socioeconomic indicators, and assessing their relation with LOS. METHODS:: In a cross-sectional study we collected area-based socioeconomic deprivation indicators from French census databases and individual ones from the 2009 medical and administrative databases of a French referral maternity hospital. The principal outcome was the LOS for delivery. Individual level socioeconomic deprivation indicators included preferential insurance scheme (health insurance allocated to poor persons). Nine area-based socioeconomic deprivation indicators were aggregated at the census tract and commune levels. The relation between socioeconomic deprivation and LOS was studied using multilevel models. The well-documented relation between socioeconomic deprivation and preterm delivery was firstly studied in these models as a validation step. RESULTS:: The linkage between aggregated and individual data was possible for the 3471 women included. The median LOS was 5 days. In multivariable analysis adjusted for age (P=0.02), twinning (P=0.0001), delivery mode (P<0.0001), drug addiction (P<0.0001), diagnosis-related group severity level (P<0.0001), and unemployment rate (P=0.002) were associated with an increased LOS. CONCLUSIONS:: Identifying deprived patients in hospital databases using routinely collected area-based indicators is feasible. The relation of these latter with LOS is consistent with previous studies. Further multicenter investigations are needed to confirm the interest of using such indicators for cost and morbidity predictions. HubMed – addiction


Dysfunctional oxidative phosphorylation makes malignant melanoma cells addicted to glycolysis driven by the V600EBRAF oncogene.

Oncotarget. 2013 Apr 8;
Hall A, Meyle KD, Lange MK, Klima M, Sanderhoff M, Dahl C, Abildgaard C, Thorup K, Moghimi SM, Jensen PB, Bartek J, Guldberg P, Christensen C

Oncogene addiction describes how cancer cells exhibit dependence on single oncogenes to escape apoptosis and senescence. While oncogene addiction constitutes the basis for new cancer treatment strategies targeting individual kinases and pathways activated by oncogenic mutations, the biochemical basis for this addiction is largely unknown. Here we provide evidence for a metabolic rationale behind the addiction to V600EBRAF in two malignant melanoma cell lines. Both cell lines display a striking addiction to glycolysis due to underlying dysfunction of oxidative phosphorylation (OXPHOS). Notably, even minor reductions in glycolytic activity lead to increased OXPHOS activity (reversed Warburg effect), however the mitochondria are unable to sustain ATP production. We show that V600EBRAF upholds the activity of glycolysis and therefore the addiction to glycolysis de facto becomes an addiction to V600EBRAF. Finally, the senescence response associated with inhibition of V600EBRAF is rescued by overexpression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), providing direct evidence that oncogene addiction rests on a metabolic foundation. HubMed – addiction


Potential Therapeutic Uses of Mecamylamine and its Stereoisomers.

Pharmacol Biochem Behav. 2013 Apr 17;
Nickell JR, Grinevich VP, Siripurapu KB, Smith AM, Dwoskin LP

Mecamylamine (3-methylaminoisocamphane hydrochloride) is a nicotinic parasympathetic ganglionic blocker, originally utilized as a therapeutic agent to treat hypertension. Mecamylamine administration produces several deleterious side-effects at therapeutically relevant doses. As such, mecamylamine’s use as an antihypertensive agent was phased out, except in severe hypertension. Mecamylamine easily traverses the blood-brain barrier to reach the central nervous system (CNS), where it acts as a nicotinic acetylcholine receptor (nAChR) antagonist, inhibiting all known nAChR subtypes. Since nAChRs play a major role in numerous physiological and pathological processes, it is not surprising that mecamylamine has been evaluated for its potential therapeutic effects in a wide variety of CNS disorders, including addiction. Importantly, mecamylamine produces its therapeutic effects on the CNS at doses 3-fold lower than those used to treat hypertension, which diminishes the probability of peripheral side-effects. This review focuses on the pharmacological properties of mecamylamine, the differential effects of its stereoisomers, S(+)- and R(-)-mecamylamine, and the potential for effectiveness in treating CNS disorders, including nicotine and alcohol addiction, mood disorders, cognitive impairment and attention deficit hyperactivity disorder. HubMed – addiction


The plasma levels of the cytokines in opium-addicts and the effects of opium on the cytokines secretion by their lymphocytes.

Immunol Lett. 2013 Apr 18;
Nabati S, Asadikaram G, Arababadi MK, Shahabinejad G, Rezaeian M, Mahmoodi M, Kennedy D

The aim of this study was to evaluate the effects of opium addiction on the secretion of IL-4, IFN-?, IL-6 and TGF-? under In Vivo and In Vitro conditions. The blood samples were collected and PBMCs were cultured in RPMI1640 with and without opium for 48hours. The levels of the cytokines were measured using ELISA technique. The results showed that plasma levels of IL-4 and IFN-? were significantly lower and IL-6 and TGF-? were higher in plasma taken from opium-addicted subjects. The concentrations of all the cytokines in opium addicted subjects inInVitrocondition were significantly lower than the control group. Addicted subjects cultured lymphocytes significantly decrease secreted IL-4, IL-6 and TGF-? but not IFN-? in response to being cultured with opium, where as IFN-? was increased in controls. These results may explain the frequent microbial infections and an increased tumor incidence seen in addicted patients. HubMed – addiction



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