Serotonin transporter gene promoter methylation status correlates with in vivo prefrontal 5-HTT availability and reward function in human obesity.

A polymorphism in the promoter region of the human serotonin transporter (5-HTT)-coding SLC6A4 gene (5-HTTLPR) has been implicated in moderating susceptibility to stress-related psychopathology and to possess regulatory functions on human in vivo 5-HTT availability. However, data on a direct relation between 5-HTTLPR and in vivo 5-HTT availability have been inconsistent. Additional factors such as epigenetic modifications of 5-HTTLPR might contribute to this association. This is of particular interest in the context of obesity, as an association with 5-HTTLPR hypermethylation has previously been reported. Here, we tested the hypothesis that methylation rates of 14 cytosine-phosphate-guanine (CpG) 5-HTTLPR loci, in vivo central 5-HTT availability as measured with [11C]DASB positron emission tomography (PET) and body mass index (BMI) are related in a group of 30 obese (age: 36±10 years, BMI>35 kg/m2) and 14 normal-weight controls (age 36±7 years, BMI<25 kg/m2). No significant association between 5-HTTLPR methylation and BMI overall was found. However, site-specific elevations in 5-HTTLPR methylation rates were significantly associated with lower 5-HTT availability in regions of the prefrontal cortex (PFC) specifically within the obese group when analyzed in isolation. This association was independent of functional 5-HTTLPR allelic variation. In addition, negative correlative data showed that CpG10-associated 5-HTT availability determines levels of reward sensitivity in obesity. Together, our findings suggest that epigenetic mechanisms rather than 5-HTTLPR alone influence in vivo 5-HTT availability, predominantly in regions having a critical role in reward processing, and this might have an impact on the progression of the obese phenotype.

A study of wrist-worn activity measurement as a potential real-world biomarker for late-life depression.

BACKGROUND: Late-life depression (LLD) is associated with a decline in physical activity. Typically this is assessed by self-report questionnaires and, more recently, with actigraphy. We sought to explore the utility of a bespoke activity monitor to characterize activity profiles in LLD more precisely. METHOD: The activity monitor was worn for 7 days by 29 adults with LLD and 30 healthy controls. Subjects underwent neuropsychological assessment and quality of life (QoL) (36-item Short-Form Health Survey) and activities of daily living (ADL) scales (Instrumental Activities of Daily Living Scale) were administered. RESULTS: Physical activity was significantly reduced in LLD compared with controls (t = 3.63, p < 0.001), primarily in the morning. LLD subjects showed slower fine motor movements (t = 3.49, p < 0.001). In LLD patients, activity reductions were related to reduced ADL (r = 0.61, p < 0.001), lower QoL (r = 0.65, p < 0.001), associative learning (r = 0.40, p = 0.036), and higher Montgomery-Åsberg Depression Rating Scale score (r = -0.37, p < 0.05). CONCLUSIONS: Patients with LLD had a significant reduction in general physical activity compared with healthy controls. Assessment of specific activity parameters further revealed the correlates of impairments associated with LLD. Our study suggests that novel wearable technology has the potential to provide an objective way of monitoring real-world function.