Illness recognition and disruptiveness in psychotic illness.

A case control investigation was performed to examine the relatively high rate of unrecognized psychotic illness within an extended family with a high-density of psychotic illness and identify factors related to nonrecognition. The study was conducted within the catchment area of a Regional Mental Health Center in central Israel. Subjects were recruited using clinic records indicating multiple family members with mental illness. Additional subjects were recruited in the homes of the subjects through family members. A total of 247 subjects were recruited, 111 of whom were determined to suffer from a psychotic disorder based on criteria in standard use. Sixty-six subjects were members of a single extended family (clan) and 181 subjects were members of nonrelated families residing in the same geographic area. While the rate of unrecognized psychotic illness was insignificant among the members of the families not related to the clan, among clan members the rate of unrecognized psychotic illness was 45%. Among this clan, recognition of psychotic illness appeared to be directly related to disruptive behavior. Additionally, it was found that, overall, subjects were more likely to recognized by the mental health system if they had fewer ill family members and more education. We conclude that although nonrecognition of mental illness does not appear to be a problem among the families in the area who are not related to the particular clan, within the clan a particular subculture appears to have developed in which perceived need for psychiatric services is related to disruptive behavior. A high density of psychotic illness within a family and less education may create a family environment that becomes tolerant of psychotic symptoms that are not disruptive to others, resulting in nonrecognition of nondisruptive illness by the mental health system.

Genome scan of Arab Israeli families maps a schizophrenia susceptibility gene to chromosome 6q23 and supports a locus at chromosome 10q24.

Schizophrenia is a complex neuropsychiatric disorder to which an as-yet-unknown number of genes contribute, interacting with each other and the environment. Linkage analyses have implicated several chromosomal regions as harboring schizophrenia susceptibility loci although rarely at levels commensurate with proposed thresholds for genome-wide significance. We systematically recruited Arab Israeli families multiply affected with schizophrenia from the catchment area of a Regional Mental Health Center. Clinical diagnoses were established by semistructured interviews and all other available sources of information under narrow, core and broad categories. Using 350 microsatellite markers, spaced at an average of 10.3 cM, we performed an autosomal scan in 155 subjects from 21 families. Linkage analysis employed affects only, multipoint, nonparametric (model-free) and also parametric (dominant and recessive) approaches. We detected significant evidence for a schizophrenia susceptibility gene at chromosome 6q23 with a nonparametric LOD score (NPL) of 4.60 (P=0.000004) under the broad diagnostic category and a parametric LOD score of 3.33 (dominant model). Under the core diagnostic category the NPL was 4.29 (P=0.00001) and the LOD score 4.16 (dominant model). We also detected suggestive evidence for linkage at chromosome 10q24 under the broad diagnostic category (NPL 3.24, P=0.0008; heterogeneity LOD score, dominant model 2.65, alpha=0.82). Additionally, NPL scores >2.0 were observed at chromosome 2q37, 4p15-16, 7p22, 9q21-22 and 14q11.1-11.2. The linkage we detected at chromosome 6q23 fulfills the criteria for genome-wide significance and is located approximately midway between loci suggested by a previous significant report at chromosome 6q25 and findings located more centromerically at 6q21-22.

Benzodiazepine augmentation of neuroleptics in treatment-resistant schizophrenia.

A significant minority of patients with schizophrenia fail to respond to neuroleptic medication alone. In some of these patients, adjunctive treatment with benzodiazepines may prove beneficial. Preclinical studies suggest that benzodiazepines significantly decrease brain dopamine release and turnover, perhaps by augmenting gamma-aminobutyric acid (GABA) inhibition of dopamine neuron activity. Double-blind clinical studies, however, have not conclusively established a role for benzodiazepines in the treatment of schizophrenia, and it seems likely that some patients respond favorably, whereas others do not. We review preliminary new observations that approximately half of a group of treatment-resistant patients, studied in a double-blind treatment protocol, demonstrated clinically significant antipsychotic responses to adjunctive alprazolam. We also briefly describe long-term efficacy of alprazolam in several patients whom we have followed in open-label clinical settings. Possible predictors or biological concomitants of benzodiazepine responsivity, which may aid in delineating distinct subgroups of patients, are discussed, and recommendations for future research are presented.

The etiology of schizophrenia: a replication test of the social selection vs. the social causation hypotheses.

A quasi-experimental design was used to test the social causation-social selection hypotheses for the etiology of schizophrenic disorders. It was based on first admissions to psychiatric in-patient facilities for Jerusalem Jewish residents aged 15 years and over. Data were extracted from hospital charts; diagnoses were made based on the NHSI, DSM III and RDC classificatory systems. The results showed that among the lower class the ethnically advantaged had higher rates of schizophrenic disorders than the ethnically disadvantaged. The results were statistically significant when the ethnic contrast was maximized. Though the results support the social selection hypothesis, social stress factors are not entirely ruled out.