Cognitive and Biochemical Processes in Depressed Adult Outpatients: a Test of the Circular Process Model

The circular process model is a psychobiological model of depression, in which it is postulated that catecholamines and negative cognitions interact to influence depression. Since its publication, there have been no empirical tests to support or refute the model. This study tested the model in 92 depressed adult outpatients with non-bipolar non-psychotic depression. There were no significant bivariate correlations among the biochemical and cognitive measures. However, the interactive model was supported by results of two out of three hierarchical regression analyses, in which the biochemical-by-cognitive interactive terms significantly predicted depression after the main effects of each variable were accounted for. These findings show sufficient evidence in support of the Circular Process Model to warrant further testing over the treatment period

Selective and Signal-dependent Recruitment of Membrane Proteins to Secretory Granules Formed by Heterologously Expressed von Willebrand Factor

von Willebrand factor (vWF) is a large, multimeric protein secreted by endothelial cells and involved in hemostasis. When expressed in AtT-20 cells, vWF leads to the de novo formation of cigar-shaped organelles similar in appearance to the Weibel-Palade bodies of endothelial cells in which vWF is normally stored before regulated secretion. The membranes of this vWF-induced organelle, termed the pseudogranule, are uncharacterized. We have examined the ability of these pseudogranules, which we show are secretagogue responsive, to recruit membrane proteins. Coexpression experiments show that the Weibel-Palade body proteins P-selectin and CD63, as well as the secretory organelle membrane proteins vesicle-associated membrane protein-2 and synaptotagmin I are diverted away from the endogenous adrenocorticotropic hormone-containing secretory granules to the vWF-containing pseudogranules. However, transferrin receptor, lysosomal-associated membrane protein 1, and sialyl transferase are not recruited. The recruitment of P-selectin is dependent on a tyrosine-based motif within its cytoplasmic domain. Our data show that vWF pseudogranules specifically recruit a subset of membrane proteins, and that in a process explicitly driven by the pseudogranule content (i.e., vWF), the active recruitment of at least one component of the pseudogranule membrane (i.e., P-selectin) is dependent on residues of P-selectin that are cytosolic and therefore unable to directly interact with vWF