Depression in the medically ill: an overview.

Depressive symptoms and syndromes are common in the medically ill, although they are frequently unrecognized and untreated. The authors review the epidemiology, differential diagnosis, clinical presentations, and response to treatment of this clinical problem. They address such methodological issues in the current literature in this area as the advantages and limitations of standardized assessment measures and discuss treatment modalities for depression in the medically ill, including antidepressant medication and ECT. This clinical problem warrants attention for a variety of reasons: its prevalence, associated morbidity, and treatability. Elucidation of the mechanisms of depression in the medically ill may also contribute to a broader understanding of depression in other populations.

The organization of the efferent projections of the parabrachial nucleus of the forebrain in the rat: a retrograde fluorescent double-labeling study.

The organization of the efferent projections of the parabrachial nucleus (PBN) to the forebrain has been investigated in the rat by means of combined injections of two fluorescent retrograde tracers: red fluorescent Evans Blue and a blue fluorescent mixture of 4',6'-diamidino-2-phenylindol 2 HCl and primuline. First, the distributions of retrogradely labeled neurons in the PBN after bilateral injections of tracers in the central nucleus of the amygdala (CNA) was examined. The CNA on one side of the brain was injected with one of the tracers and the CNA on the opposite side of the brain was injected with the other tracer. Next, the distributions of labeled neurons were examined after bilateral ventral medial thalamus (VMT) injections. Finally, the retrograde labeling of the PBN was studied after combined ipsilateral injections of one tracer in the CNa and the other tracer in the VMT. After the various injections, characteristic distributions of populations of labeled neurons within the PBN were seen. Double-labeled neurons were present only after bilateral VMT injections. From this it was concluded that the PBN projections to the VMT in the rat are bilateral. Based on the relative distributions of populations primarily taste information to the VMT and mainly visceral information to the CNA. This transfer of information to the forebrain is discussed.

Binding of angiotensins to rat brain tissue: structure activity relationship.

The binding of 3H-angiotensin II to a synaptosome-enriched fraction of the subcortical part of rat brain was studied. In this fraction specific high-affinity binding sites for angiotensin II were demonstrated. The binding sites were saturated at a ligand concentration of 2 X 10(-9) M. Scatchard analysis revealed a single class of binding sites with an apparent maximal binding capacity of 14 fmoles/mg of protein and an equilibrium dissociation constant, KD, of 0.9 X 10(-9) M. The specific binding at the KD concentration amounted to 59% of the total binding and was reversible. The association and dissociation rate constants (k1 and k-1) were 0.0212 nM-1 min-1 and 0.0196 min-1, respectively. Binding was dependent on both incubation time and tissue concentration in the incubation mixture. Angiotensins with biological activity in the brain, i.e., angiotensins I, II, III, and the fragments (3-8) and (4-8) competed with 3H-angiotensin II for the binding sites with IC50's of 9 X 10(-8) M, 2 X 10(-9) M, 4 X 10(-9) M, 4 X 10(-7) M and 4 X 10(-6), respectively. In the presence of 1 mM of the converting enzyme inhibitor SQ 14,225 the IC50 for angiotensin I was 2 X 10(-7) M. Competition by the biologically active fragment angiotensin (5-8) could not be demonstrated. The latter peptide, however, was highly metabolized during the incubation under the assay conditions used. The binding potency of the various angiotensins paralleled their dipsogenic and pressor potency. The present data indicate the possible physiological involvement of these binding sites as specific receptors in the actions of angiotensins in the brain.

Depressive symptoms and functional impairment in the medically ill.

Depressive symptoms of at least moderate severity were reported by more than 25% of a consecutive sample of end-stage renal disease (ESRD) patients awaiting cadaveric transplantation. Subjects with depressive symptoms in the clinically significant range were more often unemployed and were more functionally disabled than subjects with depressive symptoms of lesser severity. Depressive symptoms and functional disability were significantly correlated at lower but not higher levels of depression. Although depressed medical patients tend to be more impaired than those who are not depressed, the occurrence of depressive symptoms of clinical severity may depend upon the interaction among multiple additional factors. Clinically significant depression is not inevitable with severe medical disabilities and its occurrence should draw attention to specific individual vulnerabilities.

Cadaveric renal transplant failure: the short-term sequelae.

Quality of life was evaluated in 103 patients initially when each was placed on the waiting list for a cadaveric transplant. Patients who were not transplanted were reassessed six months after being placed on the waiting list. Patients who received a transplant were reassessed six months after the surgery. Cadaveric transplantation was performed in sixty-three patients by the time of follow-up. The mortality rate of 12.7 percent in transplanted patients after six months was more than twice that in patients who remained on the waiting list without a transplant, but this difference was not statistically significant. There was a graft failure rate of 23.6 percent among transplanted patients who survived six months. Graft failures were associated with some deterioration in subsequent physical activity (F = 5.4, p less than 0.03) but not in psychosocial functioning. Successful cadaveric transplants were associated with a marked and significant improvement in psychosocial well-being (F = 10.5, p less than 0.002) after six months even though physical activity did not increase. These findings suggest that 1) a successful cadaveric transplant is associated with an improved quality of life, 2) the graft failure rate of 23 percent with cadaveric transplantation is still appreciable but 3) graft failure is not necessarily associated in the short term with deterioration in psychosocial well-being.