Executive dysfunction in geriatric depression

OBJECTIVE: The purpose of this study was to characterize the neuropsychological presentation of geriatric depression and to determine whether depression-related executive dysfunction is more pronounced during advanced age. METHOD: The attention and executive functioning of 40 adults with major depression were compared with those of 40 healthy comparison subjects; 20 subjects were 20-60 years old, and 20 were > or =61 years. It was hypothesized that depressed subjects, regardless of age, would perform more poorly than comparison subjects on both attention and executive tasks but that the older depressed adults would evidence significantly greater impairment on executive measures. RESULTS: A significant interaction between age and depressive status was noted for tasks of executive functioning, while no age-depression interaction was found for tasks of selective or sustained attention. Older depressed adults demonstrated the slowest psychomotor speed and the poorest performance on tasks requiring set shifting, problem solving, and initiation of novel responses. CONCLUSIONS: Patients with late-life depression have significant impairment in executive functioning. These findings can guide the development of stimulated functional neuroimaging paradigms that may clarify the pathophysiology of geriatric depression. Timely identification of attentional and executive processes fundamental to the daily functioning of depressed older adults may lead to compensatory strategies that will improve the outcomes of late-life depression.     

Predictors of early recovery from major depression among persons admitted to community-based clinics: an observational study

BACKGROUND: Twenty years have elapsed since the National Institute of Mental Health Collaborative Depression Study reported on the early course and treatment of major depression within the mental health sector. Using similar methods, an observational study was conducted to assess relationships between initial depression severity, personality dysfunction and other baseline characteristics, subsequent treatment, and 3-month outcomes among persons admitted to public and voluntary sector outpatient clinics, including 1 academic program. METHODS: A 2-stage sampling technique was used to recruit subjects (N = 165) diagnosed by the Structured Clinical Interview for DSM-IV, Patient Version, as having a major depression episode. Sociodemographic and clinical characteristics were assessed at admission. Data on treatment and outcome were obtained at 3 months using structured instruments from the Longitudinal Interview Follow-up Evaluation. Logistic regression was used to assess hypothesized predictors of early recovery. Analyses were carried out in the total sample and after dichotomizing subjects by baseline depression severity. RESULTS: Fifty (30.3%) of the 165 subjects met recovery criteria. Less than half of the subjects (45%) met criteria for adequate pharmacotherapy. Less severe depression, having received adequate antidepressant treatment, female sex, and being married independently predicted early recovery. In the more depressed subgroup, early recovery was associated with female sex. Among less severely depressed subjects, high personality dysfunction scores and being married were significant predictors. CONCLUSIONS: Initial depression severity and receiving adequate pharmacotherapy predict early recovery in individuals with major depression seeking outpatient treatment. A minority of persons receive intensive antidepressant treatment. Less severe personality dysfunction and being married predicts early recovery among persons with less severe depression.     

Treatment of idiopathic membranous nephropathy (IMN)

The best treatment of idiopathic membranous nephropathy remains an area of clinical controversy. At the moment only patients with nephrotic syndrome and/or declining renal function should be treated. Despite the negative trials, prolonged oral administration of corticosteroids alone may be a safe and an effective first-line treatment in nephrotic patients. If corticosteroids are ineffective, prolonged use of cyclosporine in low-doses can be recommended as an alternative treatment, that diminishes rapidly proteinuria in the majority of patients. Both treatments (intravenous high doses of corticosteroids and cyclosporine) may also be effective in patients with declining renal function. Because of their toxicity, the routine use of alkylating agents for patients with nephrotic syndrome is not justified. They may be retained for patients, in whom other treatment modalities have failed. Chlorambucil may be preferred over cyclophosphamide since it carries less toxicity. A lower dose of chlorambucil, than that usually suggested, for a short period of time seems to be prudent in an effort to avoid serious side-effects.     

Hyperthyroxinaemia in hepatocellular carcinoma: relation to thyroid binding globulin in the clinical and preclinical stages of the disease

Serum thyroxine was significantly higher in 59 patients with hepatocellular carcinoma than in normal subjects, patients with uncomplicated cirrhosis (48), or other primary tumours with or without hepatic metastases (50). Elevated thyroxine levels appeared attributable to high levels of thyroxine binding globulin which showed a positive linear correlation with serum thyroxine in all groups studied. Despite this hyperthyroxinaemia all patients appeared clinically euthyroid and, consistent with this, T3 was elevated in only one patient and the free thyroxine index was normal in all. Amongst a group of 25 cirrhotic patients who were followed-up for between 12 and 72 months, there was a striking dissociation between the TBG values of those destined to develop HCC and those who did not. In the former group TBG rose steadily with time whereas in the latter group levels remained stable, or, more often, fell. The rises in TBG occurred prior to any clinical signs of tumour development and may be one of the earliest serological changes to occur during carcinogenesis in the cirrhotic liver.     

Multiple cutaneous acral metastases in a woman with breast adenocarcinoma treated with pegylated liposomal doxorubicin: incidental or aetiological association?

This paper reports the case of a 45-year-old female with histologically documented, multiple cutaneous metastases in the palmar and plantar surface of the fingers and toes originating from a breast adenocarcinoma after treatment with a docetaxel and pegylated liposomal doxorubicin regimen. The rarity of such a metastatic pattern from breast cancer and the eventual association with the chemotherapy administered are thoroughly discussed.     

Depression in the elderly

In elderly people, depression mainly affects those with chronic medical illnesses and cognitive impairment, causes suffering, family disruption, and disability, worsens the outcomes of many medical illnesses, and increases mortality. Ageing-related and disease-related processes, including arteriosclerosis and inflammatory, endocrine, and immune changes compromise the integrity of frontostriatal pathways, the amygdala, and the hippocampus, and increase vulnerability to depression. Heredity factors might also play a part. Psychosocial adversity-economic impoverishment, disability, isolation, relocation, caregiving, and bereavement-contributes to physiological changes, further increasing susceptibility to depression or triggering depression in already vulnerable elderly individuals. Treatment with antidepressants is well tolerated by elderly people and is, overall, as effective as in young adults. Evidence-based guidelines for prevention of new episodes of depression are available as are care-delivery systems that increase the likelihood of diagnosis, and improve the treatment of, late-life depression. However, in North America at least, public insurance covers these services inadequately.     

Mitochondrial genome mutations in hypertensive individuals

Human essential hypertension (HTN), a polygenic, multifactorial, and highly heterogeneous disorder of unknown etiology, has been shown to have excess maternal transmission in several studies, suggesting a possible mitochondrial involvement. In an effort to assess the contribution of the mitochondrial genome to HTN we initiated a systematic, extended screening of hypertensive individuals to identify potentially pathogenic mtDNA mutations. We applied our newly developed novel class of tests for the detection of mitochondrial mutation involvement in complex diseases to the hypertension data set from 350 pedigrees of white ethnicity and 98 of African American ethnicity ascertained at HTN clinics associated with Boston Medical Center, and we identified families with a likely mitochondrial involvement. We analyzed the sequence of the entire mitochondrial genome in probands from 20 such pedigrees, consisting of 10 African American and 10 white families. Comparison with the reference "Cambridge" sequence revealed a total of 297 base changes, including 24 in the ribosomal RNA (rRNA) genes, 15 in the transfer RNA (tRNA) genes, and 46 amino acid substitutions, with the remainder involving the noncoding regions or synonymous changes. Among the coding region mutations, 30 are novel, with 13 hypertensive probands carrying at least one novel variant, usually in combination with the previously described common polymorphisms, several of which are associated with cardiovascular and renal pathologies. These data will serve as a starting point for large-scale case-control association studies.