A picture is worth a thousand words: effects of emotional distracters on executive task performance

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Aberrant functional connectivity of cortico-basal ganglia circuits in major depression

ManuscriptThere is considerable evidence of functional abnormalities of the cortico-basal ganglia circuitry in affective disorders. However, it has been unknown whether this represented primary pathology within these circuits or altered activation as a result of aberrant input from other brain regions. The aim of this study was to test the hypothesis that cortico-basal ganglia circuit dysfunction represents primary pathology in unipolar depression. Eighteen male subjects with recurrent unipolar depression and eighteen controls without psychiatric illness were studied using functional MRI and functional connectivity analyses. All unipolar subjects were unmedicated and without current psychiatric comorbidity. Compared to controls, unipolar subjects exhibited altered connectivity between bilateral subcortical components of the circuitry (putamen-thalamus) and left hemisphere input and output components. Results provided evidence that functional abnormalities of these circuits represent primary pathology. Further, we found that age of onset but not duration of illness impacts circuit function. These findings suggest that the cortico-basal ganglia circuitry is likely one of several loci of primary pathology in major depression. Additionally, early age of onset is associated with greater circuit abnormality and as such may impact clinical characteristics and/or treatment response through a mechanism of decreasing functional connectivity of some circuit segments. Finally, altered cortico-basal ganglia circuit connectivity with cortical regions (anterior cingulate, inferior frontal gyrus and sensorimotor) may contribute to the emotional dysregulation, impaired emotional recognition and psychomotor symptoms associated with unipolar illness

The transcriptional landscape of age in human peripheral blood

Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify 1,497 genes that are differentially expressed with chronological age. The age-associated genes do not harbor more age-associated CpG-methylation sites than other genes, but are instead enriched for the presence of potentially functional CpG-methylation sites in enhancer and insulator regions that associate with both chronological age and gene expression levels. We further used the gene expression profiles to calculate the 'transcriptomic age' of an individual, and show that differences between transcriptomic age and chronological age are associated with biological features linked to ageing, such as blood pressure, cholesterol levels, fasting glucose, and body mass index. The transcriptomic prediction model adds biological relevance and complements existing epigenetic prediction models, and can be used by others to calculate transcriptomic age in external cohorts.Peer reviewe