Psychiatric aspects of murder and attempted murder.

The clinical data and forensic aspects of 28 individuals charged with murder and 10 charged with attempted murder examined over the last 35 years are recorded. The majority of those aged 40 years or over were criminally insane. A positive family history of psychiatric illness was present in the majority of the criminally insane group. Murder and attempted murder in the setting of a stable marriage was almost invariably the result of serious psychiatric illness. After the clearcut cases of schizophrenia and depressive illness were separated there were left a mixed paranoid group and a large group of individuals with severe personality disorders. Of the forensic aspects a case is made for the wider use of "unfitness to plead" in the severely psychotic. The follow-up of cases strongly suggested that those found not guilty on psychiatric grounds were likely to be held for longer periods than those treated as criminals. The author suggests that the public would be better protected if the Crown sought an insanity verdict in some cases rather than oppose it.     

Encoding,remembering and awareness in lorazepam-induced amnesia

The effects of lorazepam (1,2 mg) and placebo on encoding, remembering and awareness were assessed in a study with 54 healthy volunteers. All subjects studied stimulus materials in a levels of processing (L-o-p) task. Half the subjects were assessed on an explicitmemory task of word recognition and the other half were given an implicit memory task of word-stem completion. Following the implicit task, awareness of retrieval was further investigated by questions and by subjects' recollective experience in recognising the actual words they had completed from stems. L-o-p effects and marked lorazepam-induced impairments were found in the implicit task of word-stem completion although the interaction between L-o-p and drug effects emerged only as a trend in the data. Lorazepam-induced impairments on stem-completion may then be explained at least in part as being due to contamination by explicit retrieval processes, but we cannot rule out the possible role of drug effects on perceptual processes at encoding. Results from responses to awareness questions and from analysis of subsequent recollective experience indicated that subjects were not aware of using explicit retrieval during the implicit task. Results also replicated previous findings showing that both lorazepam and L-o-pindependently affect performance in an explicit memory task of word recognition. Thus drug-induced deficits at encoding persist regardless of the level at which information is initially processed.     

Benzodiazepines,amnesia and sedation: Theoretical and clinical issues and controversies

The amnestic effect of benzodiazepines, first described in 1965, and the subsequent attempts to identify the precise nature of this effect, are reviewed. The difficulty in deciding to what extent this effect is secondary to the sedative action of these drugs is shown by the lack of agreement between studies. Nevertheless, it is concluded that, given the right experimental design, all benzodiazepines can be shown to cause an anterograde amnesia which is probably primarily a result of reduced attention or rehearsal and secondary to sedation. Its onset, degree and duration are influenced by dose, rate of absorption, route of administration, potency and the receptor occupancy rate of the particular benzodiazepine involved, but plasma elimination t_½ appears to be relatively unimportant. The clinical relevance of this for the long-term use of hypnotics and anxiolytics is not clear. Tolerance appears to be greater than for the anxiolytic but less than the sedative or anticonvulsant effect of benzodiazepines. It seems that transient amnestic effects could occur in chronic users related to post-dose, peak benzodiazepine levels. The great variability in individual response means that transient amnesia is a potential adverse drug reaction in certain individuals taking benzodiazepines.     

Phosphatidylserine reverses reserpine-induced amnesia

The effects of phosphatidylserine (PS) were studied in rats treated with reserpine (1 mg/kg) immediately after training in the passive avoidance task. In experiment I, phosphatidylserine (25 mg/kg) was administered 30 min before or immediately after training. Acute pre- or post-treatment with phosphatidylserine was effective in reversing the amnestic effect of reserpine in test trials performed 24 h and 1 week after training. Experiment II was performed to determine if the long-term pretreatment with phosphatidylserine (25 mg/kg) for 7 days is able to protect the rats against the amnestic effects of reserpine in this task. The data show that phosphatidylserine reverses the impairment induced by reserpine in trials performed 24 h and 1 week after training. These results indicate that the memory deficits associated with catecholamine depletion caused by reserpine can be attenuated by acute pre- or post-training or by long-term pretreatment with this phospholipid.     

Effects of 4-hydroxy, 4-phenyl,caproamide on pentylenetetrazol-induced amnesia

Early reports suggest a relationship between pentylenetetrazol-induced convulsions (PTZ) and amnesia. 4,-Hydroxy, 4-phenyl caproamide (YPCA) is potently anticonvulsant againts PTZ-induced convulsions. The purpose of these experiments is to show the possible role of PTZ in these amnestic effects. Experiment 1 proves YPCA antagonism of PTZ-induced convulsions in mice. Experiment 2 shows how YPCA, injected before PTZ and after animal training, protects against convulsions, leaving memory storage un-affected. However, when YPCA is injected before training (10 and 5 min) and PTZ 15 min afterwards (5 and 10 min after training), a retention impairment was observed. The results are discussed in terms that emphasize the need of convulsions in retrogarde amnesia. Experiment 3 shows that foot shock is necessary for passive avoidance acquisition. Experiment 4 shows that subconvulsive doses of PTZ (5, 10, 20, and 40 mg/kg^-1) have no effect on memory.     

Temporal and pharmacological parameters of puromycin-induced amnesia

Mice were trained in step-down passive avoidance behavior. Bitemporal injections of puromycin (PM) were given either immediately or delayed until 24 hrs after training. PM produced a marked amnesia in both cases during retention testing 3 days later. The amnesia persisted during a second retention test 6 days after training. Of all the antibiotics, only PM is effective as an amnestic agent when injections are delayed 24 or more hours after training. Cycloheximide (CXM) was also injected bitemporally immediately after training. However, CXM produced a weaker amnestic effect even though it produced a much greater inhibition of cerebral protein synthesis, more rapidly, and of longer duration. In an effort to attenuate the amnesia produced by PM, in separate experiments, the mice were injected with combined injections of PM and CXM (bitemporally); mice were also given combined injections of PM (bitemporally) and amphetamine (subcutaneously). The amnesia produced by immediate injections of PM was not attenuated by either CXM or amphetamine. However, the amnesia produced by delayed injections of PM was attenuated by both CXM and amphetamine. These results suggest that delayed injections of PM (24 hours after training) block the e expression or retrieval of memory. This study also supports the contention that puromycin has two separate effects on memory with different temporal parameters depending on when the drug is injected relative to initial training.     

The thrill can kill: murder by methylation

Why babies of crack-cocaine mothers develop heart problems has always been a mystery. In this issue of Molecular Pharmacology, Zhang et al. (p. 1319) show that a specific methylation occurs at the protein kinase Cepsilon (PKCepsilon) promoter of the babies born of mother rats exposed to cocaine. This reduces the expression of PKCepsilon, a naturally cardioprotective enzyme, which provides a plausible molecular mechanism for cardiac failure.