The link between depressive symptoms, negative cognitive bias and memory complaints in older adults.

OBJECTIVES: We sought to examine the relationship between depressive symptoms and subjective memory problems. We hypothesized that the relationship between depressive symptoms and poor subjective memory functioning is mediated by negative cognitive bias that is associated with hopelessness, a wish to die and low self-esteem. METHODS: Complete data were available for 299 older adults with and without significant depressive symptoms who were screened in primary care offices and invited to participate, completed a baseline in-home assessment. Subjective memory functioning and psychological status was assessed with commonly used, validated standard questionnaires. RESULTS: In regression models that included terms for age, gender and cognitive measures, depressive symptoms were significantly inversely associated with the global self-assessment of memory (beta=-0.019; p=0.006). When components of negative cognitive bias were included in the model (hopelessness, low self-esteem, a wish to die), the relationship of depressive symptoms with subjective memory problems was attenuated, consistent with mediation. CONCLUSIONS: Our results suggest that assessment and successful interventions for memory complaints in non-demented older adults need to account for negative cognitive bias as well as depressive symptoms. Longitudinal research is needed to confirm our findings before a mediator relationship can be presumed.

Transcriptional regulation of the vacuolar H(+)-ATPase B2 subunit gene in differentiating THP-1 cells.

Monocyte-macrophage differentiation was used as a model system for studying gene regulation of the human vacuolar H(+)-ATPase (V-ATPase). We examined mRNA levels of various V-ATPase subunits during differentiation of both native monocytes and the cell line THP-1, and found that transcriptional and post-transcriptional mechanisms could account for increases in cell V-ATPase content. From nuclear runoff experiments, we found that one subunit in particular, the B2 isoform (Mr = 56,000), was amplified primarily by transcriptional means. We have begun to examine the structure of the B2 subunit promoter region. Isolation and sequencing of the first exon and 5'-flanking region of this gene reveal a TATA-less promoter with a high G + C content. Primer extension and ribonuclease protection analyses indicate a single major transcriptional start site. We transfected promoter-luciferase reporter plasmids into THP-1 cells to define sequences that mediate transcriptional control during monocyte differentiation. We found that sequences downstream from the transcriptional start site were sufficient to confer increased expression during THP-1 differentiation. DNase I footprinting and sequence analysis revealed the existence of multiple AP2 and Sp1 binding sites in the 5'-untranslated and proximal coding regions.