ABCB1 Polymorphism Predicts Escitalopram Dose Needed for Remission in Major Depression.

ABCB1 polymorphism predicts escitalopram dose needed for remission in major depression.

Filed under: Depression Treatment

Transl Psychiatry. 2012; 2: e198
Singh AB, Bousman CA, Ng CH, Byron K, Berk M

The ATP-binding cassette family of transporter proteins, subfamily B (MDR/TAP), member 1 (ABCB1) (P-glycoprotein) transporter is a key component of the blood-brain barrier. Many antidepressants are subject to ABCB1 efflux. Functional polymorphisms of ABCB1 may influence central nervous system bioavailability of antidepressants subject to efflux. Single-nucleotide polymorphisms (SNPs) at rs1045642 (C3435T) of ABCB1 have been associated with efflux pump efficiency. This may explain part of the interindividual variation in antidepressant dose needed to remit. Individuals (N=113) with DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) major depressive disorder (MDD) were treated with escitalopram (ESC) or venlafaxine (VEN) over 8 weeks. The17-item Hamilton Depression Rating Scale was assessed serially, blind to genotype. SNP rs1045642 of ABCB1 along with two SNPs previously reported to be in linkage disequilibrium with it (rs2032582 and rs1128503) were genotyped. Demographic features, clinical features, P450 metabolizer status and 5-HTTLPR (serotonin-transporter-linked promoter region) genotype were controlled for. Carriers of rs1045642 TT needed on average 11?mg of ESC to remit, whereas TC and CC carriers required 24 and 19?mg, respectively (P=0.0001). This equates to a 2.0- (95% confidence interval=1.5-3.4; P<0.001) fold greater ESC dose needed to remit for C carriers compared with TT carriers at rs1045642. Of VEN-treated subjects carrying TT genotype at rs1045642, 73.3% remitted compared with 12.5% for CC genotype (odds ratio=6.69; 95% confidence interval=1.72-25.9, P=0.006). These data suggest that antidepressant dose needed to remit can be predicted by an ABCB1 SNP. This has the potential clinical translation implications for dose selection and remission from MDD. HubMed – depression

Mating system and early viability resistance to habitat fragmentation in a bird-pollinated eucalypt.

Filed under: Depression Treatment

Heredity (Edinb). 2012 Nov 28;
Breed MF, Ottewell KM, Gardner MG, Marklund MH, Stead MG, Harris JB, Lowe AJ

Habitat fragmentation has been shown to disrupt ecosystem processes such as plant-pollinator mutualisms. Consequently, mating patterns in remnant tree populations are expected to shift towards increased inbreeding and reduced pollen diversity, with fitness consequences for future generations. However, mating patterns and phenotypic assessments of open-pollinated progeny have rarely been combined in a single study. Here, we collected seeds from 37 Eucalyptus incrassata trees from contrasting stand densities following recent clearance in a single South Australian population (intact woodland=12.6 trees ha(-1); isolated pasture=1.7 trees ha(-1); population area=10?km(2)). 649 progeny from these trees were genotyped at eight microsatellite loci. We estimated genetic diversity, spatial genetic structure, indirect contemporary pollen flow and mating patterns for adults older than the clearance events and open-pollinated progeny sired post-clearance. A proxy of early stage progeny viability was assessed in a common garden experiment. Density had no impact on mating patterns, adult and progeny genetic diversity or progeny growth, but was associated with increased mean pollen dispersal. Weak spatial genetic structure among adults suggests high historical gene flow. We observed preliminary evidence for inbreeding depression related to stress caused by fungal infection, but which was not associated with density. Higher observed heterozygosities in adults compared with progeny may relate to weak selection on progeny and lifetime-accumulated mortality of inbred adults. E. incrassata appears to be resistant to the negative mating pattern and fitness changes expected within fragmented landscapes. This pattern is likely explained by strong outcrossing and regular long-distance pollen flow.Heredity advance online publication, 28 November 2012; doi:10.1038/hdy.2012.72.
HubMed – depression

Outcomes Following Hip Fracture Surgery: A 2-Year Prospective Study.

Filed under: Depression Treatment

Am J Geriatr Psychiatry. 2012 Nov 22;
Burns A, Younger J, Morris J, Baldwin R, Tarrier N, Pendleton N, Cohen P, Horan M, Banerjee S

OBJECTIVES:: To describe the health outcomes in older people following hip fracture surgery. DESIGN, SETTING, AND PARTICIPANTS:: A naturalistic prospective study of people who had undergone hip fracture surgery undertaken in three specialist inpatient orthopaedic units in Manchester, England, with follow-up for 2 years in primary care. One hundred forty-two people, age 60 and older who had undergone hip fracture surgery of whom 74 were interviewed at follow-up. MEASUREMENTS:: Assessment of mood (using the Geriatric Depression Scale and Hospital Anxiety and Depression Scale), cognitive function (Mini-Mental State Examination), pain (Wong-Baker and McGill scales), tests of function (Up and Go Test, Gait Test and Functional Reach), and Sickness Impact Profile. RESULTS:: Twenty-six percent of the original group had died by the time of the 2-year follow-up and associated with increasing age, poorer mobility, and higher levels of support. Sixteen percent of the group were found to be depressed, the only robust predictor of this being depression at entry to the study. There was a consistency in the presence or absence of depressive symptoms over the duration of the study. Forty-nine percent were able to walk independently at 2 years. CONCLUSION:: The presence of depressive symptoms is associated with poor outcomes at 2 years. Few people recover from, or develop, depression over 2 years.
HubMed – depression

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