Abhay Singh

Advances in the understanding of the neurobiology of the nicotinic receptor have started to be matched by an appreciation of the potential role of these receptors in a variety of neuropsychiatric disorders. While alterations in nicotinic receptor number and/or function have been associated with such conditions as Alzheimer's disease for several years, there is increasing evidence that nicotinic receptor function may play a significant role in other disorders as well including schizophrenia, Parkinson's disease, anxiety disorders, and attention deficit-hyperactivity disorder (ADHD). Research in our laboratory and those of other investigators have utilized sophisticated psychopharmacological, cognitive, electrophysiological, neuroimaging and other techniques to assess the impact of nicotinic receptor modulation on the clinical expression of these disorders. This manuscript reviews data, both experimental and clinical, relating to the role of nicotine and/or nicotinic receptor function in a variety of neuropsychiatric disorders with the perspective of developing appropriate targets for therapeutic drug development.

Neurocognitive deficits are an enduring characteristic of schizophrenia, and remain prominent in patients whose positive symptoms have decreased after treatment with typical neuroleptics. Recent research has reported that olanzapine improves cognitive functioning in relapsing schizophrenia followed in an outpatient setting. Whether olanzapine will have an effect on improving cognitive function in chronic schizophrenics who have been hospitalized for long periods of time, and have shown a poor response to other conventional and atypical neuroleptics, has not been established. This study investigated cognitive function in chronic medication refractory schizophrenics who were treated with olanzapine or haloperidol in a double-blind study for 8 wk, and followed in an open olanzapine study for several additional months. Patients were evaluated with psychopathology rating scales and a battery of neuropsychological tests at baseline, end of double-blind and end of open-label phases of the study. At the end of the double-blind phase there were no significant differences between olanzapine and haloperidol, except for a trend for improvement on the Wisconsin Card Sort Test on olanzapine, which was significant at traditional but not corrected significance levels. After an additional 3 months of treatment with olanzapine doses of 20-40 mg/d, our statistical analysis showed significant improvement on overall neuropsychological test performance and specific cognitive tasks assessing verbal memory. However, these open-label results are difficult to interpret definitively because of the lack of a comparison drug group and the olanzapine dose escalation over time. Neurocognitive changes were not correlated with changes in psychopathology as assessed by PANSS or SANS scores.

BACKGROUND: Point-of-care testing (POCT) devices for determining pre-donation haemoglobin (Hb) concentrations mark the advent of advanced technology for blood banks. POCT devices have undergone several improvements including changes in testing methodology and size of device, befitting the needs of blood donors and blood banks in terms of safety and quality of blood components. This study was planned to evaluate the suitability of non-invasive and invasive POCT devices for blood donor Hb screening. MATERIAL AND METHODS: Pre-donation Hb in apparently healthy blood donors was measured by a non-invasive spectrophotometric based method (NBM-200, OrSense) and an invasive method utilizing reagent free cuvettes (DiaSpect) along with a device using sodium azide-coated cuvettes (HemoControl, EKF diagnostic GmbH). The performance of the devices was evaluated by comparison with the reference method, i.e. an automated cell counter (KX-21). RESULTS: Hb was measured in 485 prospective blood donors. DiaSpect hemoglobin T system was found to be the most sensitive method of POCT for Hb (sensitivity 98.1%) followed by HemoControl (sensitivity 86.8%). NBM-200 was the least sensitive method (sensitivity 71.7%). The intraclass correlation coefficient was highest for DiaSpect (0.78), followed by HemoControl (0.77) and NBM-200 (0.43). The variation of results on repeat testing was high for NBM-200 with a coefficient of variation of 4.28%, compared to 2.19% for DiaSpect. On comparing the mean testing time, DiaSpect (1.9 seconds) was found to be significantly quicker than the other two POCT devices (p<0.001). DISCUSSION: NBM-200 has the apparent advantage of eliminating pain but also a substantial possibility of causing ineligible donors to be accepted. DiaSpect was fast and accurate, with its results showing perfect agreement with those of the standard method. It is, therefore, aptly suited for screening donors in blood banks.

Investigations into the neurobiology, and biophysical and pharmacological properties of nicotinic receptors, also known as nicotinic acetylcholine receptors (nAChRs), have led to an improved understanding of their role in a variety of neuropsychiatric disorders. There is a growing body of evidence linking alterations in nicotinic receptor number and/or function to conditions such as schizophrenia, Alzheimer's disease, Parkinson's disease, anxiety disorders, mood disorders, and attention deficit-hyperactivity disorder. The implications of nicotine receptor modulation upon the clinical expression and progression of these disorders is currently under investigation, utilizing techniques that include psychopharmacological, cognitive, electrophysiological and neuroimaging analysis. This review attempts to outline evidence pertaining to the role of the nicotinic receptor system in various neuropsychiatric disorders in the context of understanding appropriate targets for therapeutic drug development.