Frontostriatal and limbic dysfunction in late-life depression.

Studies using diverse methods have documented frontostriatal and limbic dysfunction occurring in late-life depression. Although such impairments may result from aging-induced brain changes unrelated to depression, there are at least two reasons to suggest that they play a pathogenetic role in geriatric depression. First, frontostriatal dysfunction has been identified in at least some younger depressed subjects without known neurological abnormalities. Second, frontostriatal dysfunction may be associated with poor short- and long-term outcomes of late-life depression. Relating frontostriatal and limbic dysfunction to the course of late-life depression is an appropriate way for investigating its pathophysiological relevance, given that no biological test can be used as a validating criterion. However, this approach has experimental limitations. Studies of the course of late-life depression may be influenced by selective survival of depressed patients with favorable prognosis; factors peripherally related to the biology of depression, for example, physical handicaps; and clinical factors with unclear relationship to specific biological abnormalities, for example, personality disorders. Nonetheless, studies comparing depressed patients with control subjects complemented with studies of course of illness can bring to bear the rapidly evolving cognitive-neuroscience and brain-imaging techniques in an investigation of the networks responsible for predisposing, precipitating, and perpetuating late-life depression.     

Circulating levels of ICAM-1, VCAM-1, and MCP-1 are increased in haemodialysis patients: association with inflammation, dyslipidaemia, and vascular events.

BACKGROUND: Increased levels of circulating adhesion molecules and chemokines have been reported in haemodialysis (HD) patients but the influence of the HD membranes on their secretion, as well as their pathophysiological implications, remains largely unknown. METHODS: Circulating levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and monocyte chemoattractant protein-1 (MCP-1) were measured by immunosorbent assay (ELISA) in 81 HD patients (45 male, mean age 57+/-13 years) and 35 normal subjects. All patients had been stabilized on renal replacement therapy for >3 months and were free of active infection. Thirty-three patients (40.7%) were routinely dialysed with modified cellulose membranes and 48 patients (59.3%) were dialysed with polysulfone membranes. Blood samples were taken directly from the arteriovenous fistula immediately before and at the end of a routine HD session. RESULTS: Pre-dialysis levels were significantly elevated in HD patients compared with controls (ICAM-1 515+/-177 vs 238+/-664 ng/ml, P<0.0001; VCAM-1 2107+/-648 vs 1012+/-115 ng/ml, P<0.0001; MCP-1 427+/-148 vs 125+/-42 pg/ml, P<0.0001). The HD session resulted in a significant increase in the levels of all three molecules measured (515+/-177 vs 679+/-187 ng/ml, P<0.0001; 2107+/-648 vs 2662+/-800 ng/ml, P<0.0001; 427+/-148 vs 567+/-153 pg/ml, P<0.0001, respectively). There was no difference in pre- or post-dialysis levels of the above molecules between patients routinely dialysed with either modified cellulose or polysulfone membranes. MCP-1 levels had a positive correlation with ICAM-1 levels (r=0.41, P<0.0005). VCAM-1 levels had a negative correlation with HDL levels (r=-0.30, P<0.01) and were significantly elevated in patients with HDL <35 mg/dl compared with patients with HDL > or = 35 mg/dl (2300+/-606 vs 1890+/-633 ng/ml, P<0.005). Log-transformed exact C-reactive protein (CRP) values were significantly correlated with ICAM-1 and VCAM-1 levels (r=0.41, P<0.005 and r=0.43, P<0.005, respectively). In addition, compared with patients with normal CRP values, patients with elevated CRP had significantly increased levels of ICAM-1 (466+/-166 vs 580+/-172 ng/ml, P<0.005). Patients with cardiovascular, cerebrovascular, or peripheral vascular diseases had significantly increased serum CRP and ICAM-1 levels compared with patients with no evidence of vascular disease (19.2+/-12.9 vs 7.9+/-11.8 mg/l, P<0.001 and 608+/-189 vs 474+/-155 ng/ml, P<0.005 respectively). CONCLUSIONS: Serum levels of ICAM-1, VCAM-1, and MCP-1 are increased in HD patients and probably result from either inadequate clearance or enhanced synthesis and release. HD session resulted in a significant increase of the above molecule levels but the exact mechanism(s) responsible for these alterations are yet to be fully elucidated. Increased levels of adhesion molecules are associated with inflammation, dyslipidaemia, and cardiovascular events. However, the potential link between these processes and its clinical significance warrants further investigation.     

Comorbidity of depression with other medical diseases in the elderly.

A major factor in the context of evaluating depression in the elderly is the role of medical problems. With aging there is a rapid increase in the prevalence of a number of medical disorders, including cancer, heart disease, Parkinson's disease, Alzheimer's disease, stroke, and arthritis. In this article, we hope to bring clarity to the definition of comorbidity and then discuss a number of medical disorders as they relate to depression. We evaluate medical comorbidity as a risk factor for depression as well as the converse, that is, depression as a risk factor for medical illness. Most of the disorders that we focus on occur in the elderly, with the exception of HIV infection. This review focuses exclusively on unipolar disorder. The review summarizes the current state of the art and also makes recommendations for future directions.     

A role for extracellular Na+ in the channel gating of native and recombinant kainate receptors

Ionotropic glutamate receptors of the kainate and AMPA subtypes share a number of structural features, both topographical and in terms of stoichiometry. In addition, AMPA and kainate receptors share similar pharmacological and biophysical properties in that they are activated by common agonists and display rapid activation and desensitization characteristics. However, we show here that in contrast to AMPA receptor-mediated responses (native or recombinant GluR3 receptor), the response of native and recombinant (GluR6) kainate receptors to glutamate was drastically reduced in the absence of extracellular Na+ (i.e., when replaced by Cs+). Removal of Na+ increases the rate of desensitization, indicating that external Na+ modulates channel gating. Whereas the size of the substituting cation is important in mimicking the action of Na+ (Li+>K+>Cs+), modulation was voltage independent. These results indicate the existence of different gating mechanisms for AMPA and kainate receptors. By using chimeric AMPA-kainate receptors derived from GluR3 and GluR6, we have identified a key residue in the S2 segment of GluR6 (M770) that is largely responsible for the sensitivity of the receptor to external Na+. Thus, these results show the existence of a specific kainate receptor gating mechanism that requires external Na+ to be operative.     

Frontal signal hyperintensities in mania in old age.

OBJECTIVE: Signal hyperintensities (SH) on magnetic resonance (MR) imaging have been associated with increased age and with mood disorders. Frontal and subcortical neuropathology has been implicated in the pathophysiology of mania and bipolar disorders. The authors assessed frontal and subcortical SH in elderly bipolar manic patients and the comparison group, and hypothesized that SH scores would be greater in the patient group. METHOD: MR imaging was performed in patients aged > or = 60 years with bipolar disorder, mania, and in a same-aged community comparison group. SH were rated blindly using the Boyko system. Frontal deep white matter and basal ganglia SH were assessed in the left and right hemispheres. RESULTS: SH scores were significantly greater in patients (N = 40) than the comparison group (N = 15) in frontal deep white matter (left: p = 0.003; right: p = 0.023) based on Mann-Whitney two-sample exact tests. The SH scores in the subcortical gray regions overlapped in these groups. In patients, higher right frontal SH scores were associated with later age at onset of mania. CONCLUSIONS: Frontal deep white matter SH may be increased in elders with bipolar disorder. Further study of the relationship of SH to age at onset in elders is warranted.     

First Experience on the Effect of In‐feed Lincomycin for the Control of Proliferative Enteropathy in Growing Pigs

This trial's aim was to evaluate the effect of in‐feed lincomycin for the control of proliferative enteropathy (PE; also known as ileitis) in growing pigs, in which it is associated with significant morbidity levels. Investigation regarding the efficacy of this substance in growing pigs has never been carried out before in a field trial. The trial farm had a previous history of PE outbreaks. On day 1 of the trial (age of 62 ± 1.5 days), 240 pigs were divided into two groups of 120 pigs/group which were allocated into five pens of 24 pigs each. Therefore, a randomized block design was used with two experimental groups (T1–T2) and five replicates (pens) per group. T1 group served as negative control (NC) animals which were receiving no medication and conversely T2 group received in‐feed lincomycin at the dose of 110 mg/kg of feed. The treatment period lasted for 3 weeks, followed by an observation period of 4 weeks up to the age of 111 ± 1.5 days which was the end of the grower stage. Administration of lincomycin at a dose of 110 mg/kg of feed had beneficial effects compared with the NC group. The pigs of T2 group showed significant improvement of their production parameters in terms of average daily body gain (ADG) and feed conversion ratio (FCR) not only during the treatment period (ADG: 0.515 ± 0.050 versus 0.481 ± 0.071 and FCR: 2.38 ± 0.05 versus 2.56 ± 0.08, for T2 and T1 groups respectively), but also during the remaining period until the end of the grower stage (observation period: ADG: 0.687 ± 0.019 versus 0.646 ± 0.044 and FCR: 2.58 ± 0.02 versus 2.74 ± 0.02 respectively). Other effects in the T2 group refer to the reduction of diarrhoea prevalence (mean pen diarrhoea score during the whole grower stage: 0.200 ± 0.060 versus 0.632 ± 0.041 respectively), morbidity rates (morbidity rates during the whole grower stage: 15.83% versus 45.00% respectively) and the reduction of Lawsonia intracellularis prevalence as shown by polymerase chain reaction diagnostic method (at the end of the treatment period: 10.0% versus 60.0% respectively). In conclusion, treatment with 110 mg lincomycin/kg of feed for 21 consecutive days had a beneficial effect on the control of PE in growing pigs.     

Clonidine challenge of cortisol secretion in dementia and geriatric depression

The effect of oral clonidine challenge on cortisol secretion was evaluated in seven patients with primary degenerative dementia and in seven patients with major depression. Postclonidine cortisol levels were decreased in all depressed patients and in demented patients with hypercortisolemia at baseline. Demented patients with normal cortisol levels at baseline developed increased post-clonidine cortisol levels. These preliminary findings suggest differences in noradrenergic regulation of cortisol secretion among patients with primary degenerative dementia.     

A short-term inpatient program for agitated demented nursing home residents

OBJECTIVE: This case series describes the various contributors of disruptive behavior in demented nursing home residents and outlines the necessary steps to identify and treat them. DESIGN: Evaluation of overall clinical improvement and agitation at discharge from the hospital and at follow-up. SETTING: Nursing home residents consecutively admitted to the geriatric psychiatry service of a psychiatric university hospital in the New York metropolitan area. PATIENTS: 15 elderly demented nursing home residents with agitation. MEASURES: Overall clinical improvement was assessed with the 'global assessment of functioning scale'. Agitation was evaluated with the 'brief agitation rating scale' and the 'nursing home scale for agitation'. Medication side-effects were measured with the 'Simpson-Angus scale' and the 'abnormal involuntary movement scale'. RESULTS: The patients showed significantly more overall clinical improvement at discharge compared with admission. Additionally, agitation scores were significantly lower at discharge and at follow-up compared with admission. CONCLUSION: A comprehensive medical and neurological assessment, an accurate identification of comorbid psychopathology, evaluation of drug toxicity, and a thorough history of psychotropic medication trials are essential steps for a successful treatment.