Comments on risk for schizophrenia

Recent developments have significantly furthered understanding of genetic and environmental factors affecting risk for schizophrenia. Environmental effects, such as immigration, living in a city, and substance abuse have been found to be associated with later schizophrenia. Although the highest risk for schizophrenia is still having a monozygotic twin with schizophrenia (50%), the candidate genes claimed to be associated to date only yield a very small excess risk and all of these effects (environmental and genetics) increase the risk for schizophrenia by only 2-3 fold. Thus, given the low prevalence of the disorder in the general population (0.5-1%), they are not practical in predicting future illness. One possible strategy to make the currently known risk factors for schizophrenia more useful clinically is based on findings indicating that many of the genetic and environmental risks cited above are not specific for schizophrenia, but increase risk for psychopathology in general. As up to 50% of the general population will be affected during their lifetime by a condition defined in DSM IV as psychopathology, due to this much higher base rate, factors increasing risk by 2-3 fold might become clinically relevant.     

Iron status and neurobehavioral development of premature infants.

OBJECTIVE: This study was conducted to examine the relation between iron status and neurobehavioral development in premature infants. STUDY DESIGN: Infants born before 34 weeks postmenstrual age and who were medically stable were studied. Anemia was defined as hemoglobin < or =10 g/Dl and low iron stores as a serum ferritin concentration < or =75 microg/l. The infants were classified as anemic with low ferritin (Group 1; n=18), anemic with normal ferritin (Group 2; n=14), and nonanemic with normal ferritin (Group 3; n=21). A total of 18 reflexes were behaviorally evaluated at 37 weeks postmenstrual age and "reflex scores" were compared between the groups. Higher scores reflect a greater percentage of abnormal reflexes. RESULTS: Infants in group 1 (anemia/low ferritin) had a significantly higher reflex score (51.45+/-18.32%) than infants in Group 3 (38.32+/-17.75%). Group 2 had an intermediate score (45.40+/-21.70%), but not different from the other two groups. CONCLUSION: These data indicate that low iron status, both measured by anemia and ferritin levels, is related to poorer neurobehavioral status in premature infants.     

The effects of an essential fatty acid compound and a cholecystokinin-8 antagonist on iron deficiency induced anorexia and learning deficits

Iron deficiency (ID) is among the most common nutritional diseases, causing deleterious effects that include decreases in cognitive function and weight loss. The ID also induces a reduction in the number and affinity of dopaminergic D2 receptors. The new finding that ID induces an increase in the pancreas cells, leads to the hypothesis that cholecystokinin-8 (CCK-8) is involved in the ID effects. The level of CCK-8 was higher among ID rats, compared with normal rats. The ID rats in our study were anorectic and performed poorly in learning tests (Morris water maze and passive avoidance learning). Essential fatty acids (EFA) mediate dopamine activity and have been found to rehabilitate learning deficits. Treatment with a fatty acid compound blocked both the learning deficits and the anorexia, while a CCK-8 antagonist was successful only against the anorectic effects.     

Olanzapine versus clozapine in treatment-resistant or treatment-intolerant schizophrenia

Clozapine has been the gold standard for treatment of patients with refractory schizophrenia but is associated with serious safety liabilities. This has prompted the search for therapeutic alternatives for treatment-resistant schizophrenia. The objective of this study was to compare the efficacy and safety of olanzapine versus clozapine in schizophrenic patients who failed to respond adequately to antipsychotic medication or who experienced intolerable adverse effects associated with the medication. This 18-week, randomized, double-blind, parallel study compared treatment with either olanzapine (5-25 mg/day, n=75) or clozapine (100-500 mg/day, n=72) in patients with schizophrenia who were nonresponsive to, or intolerant of, standard acceptable antipsychotic therapy. At the 18-week endpoint, no statistically significant differences were found between olanzapine and clozapine in any efficacy measure used: Positive and Negative Syndrome Scale (PANSS) total, positive, negative, or general psychopathology or Clinical Global Impression severity (CGI-S). Response rates based on the criteria of Kane et al. [Arch. Gen. Psychiatry 45 (1988) 789] were also not significantly different between olanzapine-treated (57.9%) and clozapine-treated patients (60.8%). There were no significant differences in measurements of extrapyramidal symptoms or electrocardiography, and no clinically and statistically significant changes were seen in vital signs or laboratory measures in either group. Both treatments were well tolerated. Olanzapine demonstrated similar efficacy to clozapine in patients who had failed previous treatment because of lack of efficacy (treatment resistance) or intolerable side effects (treatment intolerance). Olanzapine therefore presents a safe alternative in the treatment of refractory schizophrenia.     

Development of syndrome severity scores for pediatric epilepsy

PURPOSE: A severity rating for each of the pediatric epilepsy syndromes can contribute to a more comprehensive understanding of seizure condition severity. We describe the development of the Epilepsy Syndrome Severity Scores-Child (ESSS-C). METHODS: The Delphi Technique was used to establish severity scores for pediatric epileptic syndromes as defined by the International League Against Epilepsy (ILAE). Pediatric neurologists with expertise in epilepsy were asked to rate the severity of each syndrome on a scale of 1 to 10, considering: (a) response to medical treatment, (b) seizure severity, and (c) long-term prognosis. Syndrome severity ratings took place in four different rounds. Experts provided initial scores in rounds 1 and 2. RESULTS: Of the 18 experts who agreed to participate in the development of the scale, 12 completed all four rounds. The median served as the syndrome severity score if the mean and median agreed within 0.5. Otherwise, whichever of these two numbers was closest to the mode was selected. Syndromes that were rated with high severity scores (9 or 10) or low severity scores (1 or 2) had unanimous or near unanimous ratings. The syndromes with scores in the middle range (4 to 8) had a wider range of ratings. CONCLUSIONS: If further studies provide empirical support for the validity of these epileptic syndrome severity scores, then the ESSS-C has potential for use both clinically and in future research in the prediction of outcomes of treatments.     

Mechanisms of matrix metalloproteinase-9 and matrix metalloproteinase-2 inhibition by N-acetylcysteine in the human term decidua and fetal membranes

OBJECTIVE: The purpose of this study was to evaluate the effect of N-acetylcysteine on the activity and secretion of the matrix metalloproteinases in the decidua, amnion, and chorion and the secretion of the tissue inhibitor of matrix metalloproteinase-1. STUDY DESIGN: Samples from eight nonlaboring women were taken at elective cesarean section and incubated in an in vitro organ culture in the absence or presence of N-acetylcysteine. Matrix metalloproteinase-2 and matrix metalloproteinase-9 activity was measured with the use of gel zymography. Western blot analysis was used to measure matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase-1 secretion. Data were analyzed with the paired Student t test. RESULTS: N-acetylcysteine had a direct inhibitory effect on matrix metalloproteinase-2 and matrix metalloproteinase-9 activity, regardless of tissue origin, starting at 1.0 mmol/L. In cultured media, 20 mmol/L N-acetylcysteine inhibited matrix metalloproteinase-2 and matrix metalloproteinase-9 activity in all three tissues. A differential response was demonstrated for matrix metalloproteinase-2 secretion, depending on the tissue that was studied. Its secretion was decreased in decidua at 10 mmol/L and 20 mmol/L; in amnion, the secretion was inhibited at 0.1 mmol/L and not affected at all in chorion. Matrix metalloproteinase-9 secretion was not affected in a statistically significant manner in any tissue. In the chorion, matrix metalloproteinase-9 showed a trend toward increased secretion. Tissue inhibitor of matrix metalloproteinase-1 secretion significantly decreased in the decidua at 20 mmol/L. CONCLUSION: N-acetylcysteine, at higher concentrations, has an inhibitory effect on matrix metalloproteinase-2 and matrix metalloproteinase-9 activity, regardless of the tissue origin and the differential effect on secretion depending on the tissue and N-acetylcysteine concentration.