Assessment of a multi-assay, serum-based biological diagnostic test for major depressive disorder: a pilot and replication study.

Despite decades of intensive research, the development of a diagnostic test for major depressive disorder (MDD) had proven to be a formidable and elusive task, with all individual marker-based approaches yielding insufficient sensitivity and specificity for clinical use. In the present work, we examined the diagnostic performance of a multi-assay, serum-based test in two independent samples of patients with MDD. Serum levels of nine biomarkers (alpha1 antitrypsin, apolipoprotein CIII, brain-derived neurotrophic factor, cortisol, epidermal growth factor, myeloperoxidase, prolactin, resistin and soluble tumor necrosis factor alpha receptor type II) in peripheral blood were measured in two samples of MDD patients, and one of the non-depressed control subjects. Biomarkers measured were agreed upon a priori, and were selected on the basis of previous exploratory analyses in separate patient/control samples. Individual assay values were combined mathematically to yield an MDDScore. A 'positive' test, (consistent with the presence of MDD) was defined as an MDDScore of 50 or greater. For the Pilot Study, 36 MDD patients were recruited along with 43 non-depressed subjects. In this sample, the test demonstrated a sensitivity and specificity of 91.7% and 81.3%, respectively, in differentiating between the two groups. The Replication Study involved 34 MDD subjects, and yielded nearly identical sensitivity and specificity (91.1% and 81%, respectively). The results of the present study suggest that this test can differentiate MDD subjects from non-depressed controls with adequate sensitivity and specificity. Further research is needed to confirm the performance of the test across various age and ethnic groups, and in different clinical settings.

Test-retest reliability of DSC MRI CBV mapping in healthy volunteers.

Dynamic susceptibility contrast magnetic resonance imaging (DSC MRI) can be used to generate high resolution maps of cerebral blood volume (CBV). To determine the test-retest reliability, CBV was measured in eight volunteers on two occasions, separated by 4 weeks. The mean ratio (scan 2/scan 1) for 72 cortical regions of interest (ROIs) was 1.03, with a coefficient of variation of 14%. The correlation between the first and second scans was 0.73 (p < 0.0001; 95%). In five hand-drawn ROIs, the mean ratio was 1.08, with a coefficient of variation of 12%. The correlation between scans was 0.84 (p < 0.0001). The data presented here support the hypothesis that DSC MRI CBV mapping has acceptable test-retest reliability.

The effects of ECT on brain glucose: a pilot FDG PET study.

BACKGROUND: Regional brain activity was measured before and after electroconvulsive therapy (ECT) using [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET). METHODS: 6 patients (4 females) with major depression were free of psychotropic medications for at least 2 weeks prior to baseline FDG scans. Patients were treated with bifrontotemporal ECT, and posttreatment scans were obtained after the last treatment. RESULTS: A region of interest (ROI) analysis of absolute metabolic rate showed a decrease in CMRglu after ECT in all 61 regions examined. In 17 of the 61 regions, the decrease was significant at the p < 0.05 level. In the right parietal lobe, and the right anterior and left posterior frontal lobes, the decrease in CMRglu significantly correlated with the decrease in Hamilton Depression Rating Scale (HDRS) scores (r = 0.83, 0.82, and 0.84, respectively). The analysis of CMRglu normalized to global metabolic rate showed significant increases in 8 of 61 regions, including basal ganglia, upper brainstem, and occipital lobe. DISCUSSION: The decreases in global glucose metabolism and correlation of changes in frontal metabolism with decreases in HDRS are consistent with earlier brain imaging studies of ECT. The relative increases in CMRglu observed in regions with known dopaminergic innervation (caudate and upper brainstem) have not been previously reported.

Brain kinetics of paroxetine and fluoxetine on the third day of placebo substitution: a fluorine MRS study.

OBJECTIVE: This study tested whether a relationship exists between concentration and response following discontinuation of selective serotonin reuptake inhibitors. METHOD: Eight patients with remitted major depression who were taking 20 mg/day of either fluoxetine or paroxetine underwent placebo substitution for 3 days. Serum drug and brain fluorine levels were obtained before and after placebo substitution. RESULTS: With placebo substitution, a mean of 88% (SD=13%) of brain fluorine signal from fluoxetine (plus fluorinated metabolites) remained, compared with a mean of 38% (SD=17%) of the brain fluorine signal from paroxetine (plus fluorinated metabolites). Among patients taking paroxetine, adverse events during placebo substitution correlated highly with steady-state brain drug levels. CONCLUSIONS: The correlation of clinical effects with brain drug levels in the paroxetine group suggests that relationships between drug response and brain drug concentrations merit further investigation.

A state population-based statutory reporting of dementias.

Dementia registries have been legislated or are under discussion in at least seven states (California, Florida, Maryland, Michigan, South Carolina, Illinois, and Virginia). Future reporting requirements and recommendations for state mandated reporting systems were discussed in February 1988 at the first Alzheimer's Disease Registry Workgroup Meeting, sponsored by the University of South Carolina; Centers for Disease Control; and Alzheimer's Disease and Related Disorders Association (ADRDA). The discussion clearly demonstrated the involvement of medical record professionals in influencing future reporting decisions. As the first state population-based statutory dementia registry, the New York State Alzheimer's Disease and Other Dementias Registry has faced unique problems and developed unique solutions. Both the problems and solutions have been defined with the help of medical record professionals from a variety of reporting institutions. This input occurred through phone calls, correspondence, participation in field trials and through professional organizations. Medical record personnel will continue to play a vital role in both supplying data to the New York State registry and in conceptualizing the needs of future registries in other states.

A model for quantitative evaluation of embolic stroke therapy.

We developed a small animal embolic stroke model for pharmacological screening trials. Microspheres are injected into the carotid circulations and group embolus dose-response relationships are calculated. Emboli quantity is related to neurologic injury, and small changes in neurologic function are detectable. Rabbits tolerated twice as many microspheres when cyproheptadine-treated after embolization. This demonstrated both the sensitivity of the model and the value of serotonin antagonists in reducing neurological injury.

Chronic toxicity of Dursban (chlorpyrifos) to the fathead minnow (Pimephales promelas) and the resultant acetylcholinesterase inhibition.

Fathead minnows (Pimephales promelas) were exposed to Dursban during a chronic toxicity test for 200 days including a reproductive period of their life cycle. The fish concentrated Dursban approximately 1700 times. Survival of first-generation fish was adversely affected at 2.68 micrograms/liter within 60 days. A significant increase in deformities occurred at 2.68 micrograms/liter within 30 days. Growth was significantly reduced at 2.68 micrograms/liter within 30 days and at 1.21 micrograms/liter by 60 days. Maturation of the first-generation fish was reduced at all Dursban exposures and reproduction was significantly reduced at 0.63 micrograms/liter and above. Growth and estimated biomass of 30-day-old second-generation fish were significantly reduced at 0.12 micrograms/liter, the lowest concentration tested. Brain acetylcholinesterase (AChE) activity was significantly inhibited at 0.27 micrograms/liter and above. AChE inhibition ranged from near 10% in fish exposed at 0.12 micrograms/liter to 89% for those exposed at 2.68 micrograms/liter. Inhibition results are compared to other results demonstrated during the chronic study. The use of exposure units (exposure concentration X exposure duration) is discussed as a tool for determining the effects of organophosphate pesticides on the environment.

Five-year survey of the treatment of varicose ulcers.

Eighty-two consecutive women with varicose ulcers were treated by compression sclerotherapy; 73 (89%) of them were reviewed 46 to 69 months after treatment. The cure rate at follow-up for the whole group was 82%. In obese patients the cure rate was 76%, while in non-obese patients it was 89%. These results compare favourably with those of surgery.