A Depressive Endophenotype of Mild Cognitive Impairment and Alzheimer’s Disease.

A depressive endophenotype of mild cognitive impairment and Alzheimer’s disease.

PLoS One. 2013; 8(7): e68848
Johnson LA, Hall JR, O’Bryant SE

Alzheimer’s disease (AD) is a devastating public health problem that affects over 5.4 million Americans. Depression increases the risk of Mild Cognitive Impairment (MCI) and AD. By understanding the influence of depression on cognition, the potential exists to identify subgroups of depressed elders at greater risk for cognitive decline and AD. The current study sought to: 1) clinically identify a sub group of geriatric patients who suffer from depression related cognitive impairment; 2) cross validate this depressive endophenotype of MCI/AD in an independent cohort.Data was analyzed from 519 participants of Project FRONTIER. Depression was assessed with the GDS30 and cognition was assessed using the EXIT 25 and RBANS. Five GDS items were used to create the Depressive endophenotype of MCI and AD (DepE). DepE was significantly negatively related to RBANS index scores of Immediate Memory (B=-2.22, SE=.37, p<0.001), visuospatial skills (B=-1.11, SE=0.26, p<0.001), Language (B=-1.03, SE=0.21, p<0.001), Attention (B=-2.56, SE=0.49, p<0.001), and Delayed Memory (B=-1.54, SE = 037, p<0.001), and higher DepE scores were related to poorer executive functioning (EXIT25; B=0.65, SE=0.19, p=0.001). DepE scores significantly increased risk for MCI diagnosis (odds ratio [OR] = 2.04; 95% CI=1.54-2.69). Data from 235 participants in the TARCC (Texas Alzheimer's Research & Care Consortium) were analyzed for cross-validation of findings in an independent cohort. The DepE was significantly related to poorer scores on all measures, and a significantly predicted of cognitive change over 12- and 24-months.The current findings suggest that a depressive endophenotype of MCI and AD exists and can be clinically identified using the GDS-30. Higher scores increased risk for MCI and was cross-validated by predicting AD in the TARCC. A key purpose for the search for distinct subgroups of individuals at risk for AD and MCI is to identify novel treatment and preventative opportunities. HubMed – depression

Functional Coding Variants in SLC6A15, a Possible Risk Gene for Major Depression.

PLoS One. 2013; 8(7): e68645
Quast C, Cuboni S, Bader D, Altmann A, Weber P, Arloth J, Röh S, Brückl T, Ising M, Kopczak A, Erhardt A, Hausch F, Lucae S, Binder EB

SLC6A15 is a neuron-specific neutral amino acid transporter that belongs to the solute carrier 6 gene family. This gene family is responsible for presynaptic re-uptake of the majority of neurotransmitters. Convergent data from human studies, animal models and pharmacological investigations suggest a possible role of SLC6A15 in major depressive disorder. In this work, we explored potential functional variants in this gene that could influence the activity of the amino acid transporter and thus downstream neuronal function and possibly the risk for stress-related psychiatric disorders. DNA from 400 depressed patients and 400 controls was screened for genetic variants using a pooled targeted re-sequencing approach. Results were verified by individual re-genotyping and validated non-synonymous coding variants were tested in an independent sample (N?=?1934). Nine variants altering the amino acid sequence were then assessed for their functional effects by measuring SLC6A15 transporter activity in a cellular uptake assay. In total, we identified 405 genetic variants, including twelve non-synonymous variants. While none of the non-synonymous coding variants showed significant differences in case-control associations, two rare non-synonymous variants were associated with a significantly increased maximal (3)H proline uptake as compared to the wildtype sequence. Our data suggest that genetic variants in the SLC6A15 locus change the activity of the amino acid transporter and might thus influence its neuronal function and the risk for stress-related psychiatric disorders. As statistically significant association for rare variants might only be achieved in extremely large samples (N >70,000) functional exploration may shed light on putatively disease-relevant variants. HubMed – depression

The Bidirectional Association between Depressive Symptoms and Gait Speed: Evidence from the English Longitudinal Study of Ageing (ELSA).

PLoS One. 2013; 8(7): e68632
Demakakos P, Cooper R, Hamer M, de Oliveira C, Hardy R, Breeze E

Depressive symptoms and physical performance are inversely associated, but it is unclear whether their association is bidirectional. We examined whether the association between depressive symptoms and physical performance measured using gait speed is bidirectional.We used a national sample of 4,581 community-dwelling people aged 60 years and older from the English Longitudinal Study of Ageing (from 2002-03 to 2008-09). We fitted Generalized Estimating Equation (GEE) regression models to analyse repeated measurements of gait speed (m/sec) and elevated depressive symptoms (defined as a score of ?4 on the eight-item Center for Epidemiological Studies-Depression scale).Slower gait speed was associated with elevated depressive symptoms both concurrently and two years later. After adjustment for previous depressive symptoms and sociodemographic, clinical, lifestyle, psychosocial, and cognitive factors the concurrent association was partially explained (Odds Ratio [OR] 0.42, 95% confidence interval [CI], 0.30 to 0.59, per 1m/sec increase in gait speed) and the two-year lagged association fully (OR 0.75, 95% CI, 0.56 to 1.00). Elevated depressive symptoms were associated with slower gait speed. Full adjustment for covariates (including previous gait speed) partially explained both the concurrent (? regression coefficient [?] -0.038, 95% CI, -0.050 to -0.026, for participants with elevated depressive symptoms compared with those with no or one symptom) and the two-year lagged associations (? -0.017, 95% CI, -0.030 to -0.005). Subthreshold depressive symptoms (defined as a score of two or three on the eight-item Center for Epidemiological Studies-Depression scale) were also associated with slower gait speed. Full adjustment for covariates partially explained both the concurrent (? -0.029, 95% CI, -0.039 to -0.019, for participants with subthreshold symptoms compared with those with no or one symptom) and the two-year lagged associations (? -0.011, 95% CI, -0.021 to -0.001).The inverse association between gait speed and depressive symptoms appears to be bidirectional. HubMed – depression

A New Theory and Treatment of Depression
Dr Robert Peers, a family doctor in Melbourne, Australia, presents his new theory of depression and new treatment.