Homocysteine levels in adolescent schizophrenia patients.

Homocysteine is a sulfur containing amino acid that has been widely investigated for its putative role in cardiovascular and neuropsychiatric disorders. It has been suggested that homocysteine has implications especially in young, male schizophrenia patients. In this prospective case-control study, we compared plasma homocysteine levels in a group of adolescent schizophrenia inpatients (aged 14-21 years; n=23) to normal healthy controls (n=51). Mean plasma homocysteine levels were significantly higher in the patient group than in the control group (15.40+/-2.00 and 9.78+/-0.33 micromol/L, respectively, p<0.032). The difference was almost entirely attributable to the male schizophrenia subgroup (18.18+/-5.65 in male patients vs. 10.31+/-5.33 micromol/L in female patients). The group x sex interaction was statistically significant (p=0.0035). These data indicate that a subgroup of male adolescent schizophrenia patients has high homocysteine blood levels. The role of homocysteine in the pathophysiology of adolescent-onset schizophrenia merits further investigation.

NQO2 gene is associated with clozapine-induced agranulocytosis.

Clozapine is a dibenzodiazepine neuroleptic with atypical pharmacological and clinical profiles. Treatment with this drug may be complicated with agranulocytosis (AGR). It is likely that defective oxidative mechanism may be the cause of AGR. A candidate gene, dihydronicotinamide riboside (NRH) quinone oxidoreductase 2 (NQO2), which is involved in detoxification of drugs, was selected. This gene has been mapped to the short arm of chromosome six. The gene was studied by single-strand conformation polymorphism analysis and direct sequencing in 98 schizophrenic patients that were treated with clozapine. Eighteen of these patients developed AGR. Ten polymorphisms in the coding regions, in intron 1, and in the promoter region were found, two of which were novel. Comparisons of the polymorphisms in the first intron in AGR patients and controls suggested that this site might be connected with AGR. Quantitative reverse transcriptase-polymerase chain reaction analysis showed that the level of NQO2 mRNA is low in AGR patients compared with the control group. Such a reduction in message suggests that the NQO2 gene may be involved in the development of clozapine-induced AGR.

Human leukocyte antigen typing, response to neuroleptics, and clozapine-induced agranulocytosis in jewish Israeli schizophrenic patients.

The atypical antipsychotic agent clozapine is known to be effective in schizophrenic patients refractory to other medications; however, it induces agranulocytosis in approximately 1-2%. In Jews, this complication is associated with the haplotype HLA B38,DR4,DQ3. The aim of the present study was to determine which human leukocyte antigen (HLA) antigens are involved in clozapine-induced agranulocytosis. We performed HLA typing in 88 Jewish Israeli schizophrenic patients and in 127 ethnically matched healthy individuals. Thirty-eight patients responsive to standard antipsychotic medications were treated with haloperidol, and 50 refractory patients received clozapine. A trend was noted for elevated rates of HLA B38 among control individuals and clozapine-treated patients of Ashkenazi origin compared to individuals of non-Ashkenazi origin, but the findings failed to reach statistical significance. No association was found between HLA class I antigens and the response to haloperidol or clozapine. Neutropenia developed in two clozapine-treated patients and agranulocytosis in one. Two of these three patients were of Ashkenazi origin, and both demonstrated the HLA B38 phenotype. Although the findings did not reach a statistical significance because of the small number of patients, they may support an association between clozapine-induced neutropenia/agranulocytosis and Ashkenazi origin and the HLA B38 phenotype. The rate of agranulocytosis in our sample (2%) is similar to the usual cumulative risk of agranulocytosis but in contrast to its high frequency among Jewish American patients. One possible explanation for this difference is the high rate of Ashkenazi patients in the American sample and the preponderance of non-Ashkenazi patients in our population.

HLA-B38 and clozapine-induced agranulocytosis in Israeli Jewish schizophrenic patients.

To further substantiate reports of an association between the major histocompatibility complex subtypes and clozapine-induced agranulocytosis, HLA typing was performed in 61 Jewish Israeli schizophrenic patients, in 11 of whom agranulocytosis developed following clozapine treatment and in 50 (controls) of whom it did not. Of the 11 agranulocytosis patients, seven (63%) were of Ashkenazi origin and four (37%) of Sephardi origin. There was no difference in ethnic origin between the arganulocytosis and non-agranulocytosis groups (chi 2 = 2.4, d.f. = 1, P = 0.11), although the agranulocytosis patients had a higher frequency of the HLA B38 antigen (8/11 or 72% vs. 6/50 or 12%; chi 2 = 18.7, d.f. = 1, P < 0.001). These results suggest that major histocompatibility complex gene products could be involved in clozapine-mediated haematological complications.

Partial eating disorders in a community sample of female adolescents.

OBJECTIVES: To evaluate the validity of two definitions of partial eating disorders, the Eating Attitudes Test (EAT) and a combination of the EAT and relevant criteria of the DSM-III-R, and to examine their association with factors related to anorexia nervosa and bulimia nervosa. METHOD: Questionnaires on eating behaviors, depression, obsessionality, and impulsivity were distributed to 534 female high school students. Demographic, psychosocial, and physical parameters and the subjects' height and weight were also recorded. RESULTS: EAT scores revealed maladaptive behaviors in 18% of the subjects: the combination of the EAT and DSM-III-R criteria identified 20.8% of the subjects as having partial anorexia nervosa and 11.3% as having partial bulimia nervosa. Both definitions were significantly associated with risk factors for clinical eating disorders: high weight, weight fluctuations, dieting, menstrual disturbances, high level of depression and obsessionality, and preoccupation with eating in the family. Partial bulimics fared worse on most of these parameters. Partial anorectics were not more psychologically distressed than normal subjects. CONCLUSIONS: The validity of both definitions of partial eating disorders is supported by their similar and significant associations with known risk factors for the development of the clinical syndromes. Partial bulimics are similar to patients with bulimia nervosa in the level of many eating-related disturbances and in depression, obsessionality, and impulsivity. Partial anorectics, like anorectic patients in clinical settings, tend to minimize their problems. The relevance of partial eating disorders to the later development of the full-blown clinical entity is still not established.

Spontaneous pneumoperitoneum without peritonitis.

Spontaneous pneumoperitoneum without peritonitis is a rare phenomenon which poses a dilemma to the surgeon faced with this problem. Two such cases and their outcome are presented. The first case was caused by barotrauma during positive pressure ventilation and was treated by laparotomy. No perforated viscus was found. The second case was caused by tracheal rupture during emergency intubation and was treated by observation until complete resolution. Both patients died for reasons unrelated to the pneumoperitoneum. The mechanisms for passage of air from the chest into the abdominal cavity were through the diaphragm in the first case and along the great vessels in the second. A compilation of other etiologies of pneumoperitoneum without peritonitis as extracted from the literature is presented. In the presence of pneumoperitoneum without peritonitis and when the clinical history does not suggest perforation of a viscus, we advise performing an abdominal tap. If negative, continued observation is advised.