Sensitivity of ICD-10 diagnosis of psychotic disorders in the Israeli National Hospitalization Registry compared with RDC diagnoses based on SADS-L.

OBJECTIVE: The Israeli National Psychiatric Hospitalization Registry is a nationwide list of all psychiatric hospitalizations in the country and has been widely used as a source of data for psychiatric research. This study assessed the sensitivity of the diagnosis of psychotic disorders ( International Statistical Classification of Diseases, 10th Revision [ ICD-10 ] F20.0-F29.9) and schizophrenia ( ICD-10 F20.0-F20.9) in the Registry. METHOD: Registry discharge diagnoses of psychotic disorders ( ICD-10 F20.0-F29.9) and schizophrenia ( ICD-10 F20.0-F20.9) were compared with research diagnoses derived from best-estimate procedures based on Research Diagnostic Criteria (RDC) using structured clinical research interviews, hospital records, and family information. RESULTS: Out of 169 patients meeting RDC for psychotic disorder, 150 also had a diagnosis of psychotic disorders in the Registry, yielding a sensitivity of 0.89. Re-running this analysis for the narrow definition of schizophrenia identified 94 patients who were diagnosed with schizophrenia using RDC; 82 of those patients also had a diagnosis of schizophrenia in the Registry, yielding a sensitivity of 0.87. CONCLUSION: In 87% to 89% of cases with psychotic disorders or with schizophrenia, Registry diagnoses agreed with RDC diagnoses, a rate of agreement comparable with those of other, similar registries. Because a large number of analyses derived from this and similar national registries will be published in the coming years, this constitutes relevant information.

Linkage disequlibrium in the DTNBP1 (dysbindin) gene region and on chromosome 1p36 among psychotic patients from a genetic isolate in Israel: findings from identity by descent haplotype sharing analysis.

Several genes have been reported recently to be associated with schizophrenia and bipolar disorder. Because of the complexity of the inheritance of these disorders, there is an urgent need to replicate these findings and to search for additional candidate genes. The study of genetic isolates is a powerful technique that may overcome some of the obstacles caused by genetic heterogeneity and ambiguity of phenotype definition. Identity by descent (IBD) haplotype sharing analysis in these populations may be used to detect mutations within shared haplotypes in smaller samples of affected individuals. In this study, we used IBD haplotype sharing analysis to replicate positive linkage and association findings in psychotic disorders, and to identify other regions of interest. Fifty-two patients with major psychiatric disorders from a genetically isolated village in Israel were studied. By studying eight Y chromosome markers, we were able to confirm the oral tradition of members of this isolate regarding a common paternal origin. Three hundred fifty nine microsatellite markers on 9 candidate chromosomes were genotyped, and haplotypes were reconstructed using information from family members. Two highly significant (P < 0.0001) peaks of haplotype sharing were found. One was for psychotic patients with any diagnosis at the location of dysbindin, a gene previously associated with schizophrenia. The other peak was for patients with schizophrenia on chromosome 1p36. Thus, this study both replicates an earlier finding and points to a novel region of interest, which might be unique to this population.

Benzodiazepines in schizophrenia: prefrontal cortex atrophy predicts clinical response to alprazolam augmentation.

Benzodiazepines augment clinical responses to neuroleptics in some, but not all, treatment-refractory schizophrenic patients; however the biological predictors of response have remained unclear. Since patients with prefrontal cortex (PFC) volume loss demonstrate exaggerated subcortical dopamine responses to stress, and since benzodiazepines curtail stress-induced subcortical dopamine release in PFC-lesioned animals, we reasoned that patients with PFC volume loss might show preferential clinical responses to benzodiazepine augmentation. Five patients, who were participating in a larger four-week double-blind study of alprazolam augmentation of neuroleptics in treatment-resistant or partially treatment-resistant schizophrenia, had brain MRI scans prior to entry into the study. MRI scans were morphometrically analyzed to yield estimates of PFC grey and white matter volumes and PFC cerebrospinal fluid (CSF) volume, and these were correlated with clinical responses to alprazolam augmentation. PFC grey matter volume (adjusted for overall cranial capacity) was significantly correlated (r = 0.96, p < 0.01), in the predicted direction, with alprazolam-associated changes in total Brief Psychiatric Rating Scale ratings. PFC volume loss may represent a biological marker for benzodiazepine responsivity in schizophrenia, although the present findings are considered preliminary because of the small sample size. Mechanistic considerations and suggestions for future research are discussed.