Homicidal behavior in schizophrenia associated with a genetic polymorphism determining low catechol O-methyltransferase (COMT) activity.

Although aggressive, violent, and dangerous behavior in man has multifactorial causes, genetic factors are estimated by twin and adoption studies to substantially contribute to the development of such conduct. Recently, homozygosity of a low enzyme activity variant of the catechol O-methyltransferase (COMT) gene was reported to be associated with aggressive behavior in a group of schizophrenic patients. We observe a similar tendency in a group of 30 schizophrenic patients who were confined to a maximum-security psychiatric facility for homicide. Significant excess (46.7% versus 21.0%) homozygosity of the low activity COMTmet/met genotype was observed in 30 mostly male (28 of 30) homicidal schizophrenic patients compared with 415 control subjects (Pearson chi(2) = 10.53, P = 0.005, df = 2). No difference in COMT genotype was found between 62 nonviolent schizophrenic patients and the 415 control subjects (chi(2) = 0.963, P > 0.1, df = 2). A trend for excess (46.7% versus 25.8%) homozygosity of the low activity COMTmet/met genotype was also observed when the homicidal schizophrenic subjects were compared directly with the nonviolent schizophrenic patients (chi(2) = 4.03, P = 0.1, df = 2). Similarly, an excess of the low activity COMTmet allele was observed in homicidal versus nonviolent schizophrenic patients (chi(2) = 2.92, P = 0.087, df = 2). Similar results were obtained if only male subjects were examined. No significant difference was found between control (257 Ashkenazi and 152 non-Ashkenazi Jews) COMT genotypes in the two principal ethnic groups examined (chi(2) = 3.79, P > 0.1, df = 2). Finally, no association was observed between homicidal behavior in schizophrenic patients and the dopamine D4 exon III repeat length polymorphism (D4DR) and the serotonin transporter promoter-region polymorphism (5-HTTLPR). Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:628-633, 1999.

Homicide by schizophrenic patients in Israel.

Thirty-three schizophrenic inpatients aged 45.3 +/- 13.5 years who had been found not guilty of homicide by reason of insanity were compared with 28 schizophrenic patients matched for age, sex and duration of disease who had not committed any crime. Statistical analysis revealed a high rate in the study group of individual factors associated with aggression, such as alcohol abuse, previous contact with the police, aggressive behavior and threats (P < 0.05). Significantly more of them were also immigrants (P < 0.05). There was no between-group difference in familial factors. These findings support earlier studies indicating that schizophrenic patients with the profile of alcoholism, aggressiveness and foreign country of origin are at high risk of homicidal behavior.

Cardiovascular and respiratory consequences of tension pneumothorax.

The physiologic responses to acute pneumothorax were investigated in awake, standing sheep. Pleural pressure (Ppl) was raised in graded increments by injecting air from a 500 ml syringe into the pleural cavity of eight sheep to produce pneumothorax volumes of 0, 17, 35 and 45 ml.kg-1. At the maximum value of 45 ml.kg-1 (approximately equal to 1,400 ml), Ppl at end-expiration was raised to 10 +/- 2 mmHg (mean +/- SD) whereas end-inspiratory Ppl remained negative in half the sheep as the result of increased thoracic pressure swings. The most striking haemodynamic impairment was a 22% fall in stroke volume. Cardiac output, however, remained fixed at baseline values as a result of a 28% rise in heart rate. Although hypotension has been commonly held as a consequence of severe pneumothorax, mean systemic arterial pressure increased, rising by 19% in the entire group at the maximal pneumothorax tolerated. Pulmonary gas exchange was significantly disrupted by pneumothorax, as indicated by both a 40% fall in Pao2 and a 19% reduction in arterial oxygen content. Despite a reduction in tidal volume, the sheep initially remained eucapnic by generating an increased respiratory rate and slightly increasing minute-ventilation. However, at pneumothorax volumes of 45 ml X kg-1, the sheep were no longer able to sustain minute-ventilation and a small rise in PaCO2 followed. The reduced arterial oxygen content and the fixed cardiac output led to a progressive reduction in systemic oxygen transport.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclic AMP and GMP in the cerebrospinal fluid after high-dose haloperidol treatment.

Very high dose haloperidol treatment failed to reduce cyclic AMP in cerebrospinal fluid of schizophrenic patients, whereas phenothiazines have been reported to do so. This may represent in vivo evidence for the distinction between neuroleptics that block D1 receptors (adenylate cyclase linked) and neuroleptics that do not.

Ineffectiveness of vasopressin in the treatment of memory impairment in chronic schizophrenia.

A vasopressin derivative or placebo was administered to 21 chronic schizophrenia patients for 3 weeks in a randomized crossover double-blind design. The patients were divided into those above and below the median on baseline memory measured by the Wechsler memory scale. Vasopressin treatment did not improve memory either in those patients with below median baseline memory or in the group as a whole.

Serum and CSF levels of haloperidol by radioimmunoassay and radioreceptor assay during high-dose therapy of resistant schizophrenic patients.

Serum and cerebrospinal fluid (CSF) levels of haloperidol were measured in 12 chronic neuroleptic-nonresponsive schizophrenic patients after 1 month on 60 mg haloperidol daily and then again after 1 month on 120 mg haloperidol daily. Serum haloperidol and CSF haloperidol rose with increasing dose. Serum and CSF levels were significantly correlated. No clinical improvement was achieved despite the high serum and CSF drug levels.