Kenji Fukui

Knowledge of the epidemiology of adverse drug events (ADEs) and medication errors in psychiatric inpatients is limited outside Western countries. The nature of ADEs and medication errors are important for improving the quality of care worldwide; therefore, we conducted the Japan Adverse Drug Events Study, a series of cohort studies at several settings in Japan. This report included 448 inpatients with 22,733 patient-days in a psychiatric hospital and psychiatric units at a tertiary care teaching hospital over 1 year. Four psychiatrists and two other physicians reviewed all medical charts and related documents to identify suspected incidents. The physicians later classified those incidents into ADEs, potential ADEs, medication errors, or exclusions and evaluated the severity and preventability if the incidents were events. During the study period, we identified 955 ADEs and 398 medication errors (incidence: 42.0 and 17.5 per 1000 patient-days, respectively). Among ADEs, 1.4 %, 28 %, and 71 % were life-threatening, serious, and significant, respectively. Antipsychotics were associated with half of all ADEs. The incidence of medication errors was higher in medical care units than in acute and nursing care units (40.9, 15.6, and 17.4 per 1000 patient-days, respectively). The monitoring and ordering stages were the most common error stages (39 % and 34 % of all medication errors, respectively), and 76 % of medication errors with ADEs were found at the monitoring stage. Non-psychiatric drugs were three times as likely to cause ADEs with errors compared to psychiatric drugs. Antipsychotic use, inadequate monitoring, and treatment of physical ailments by psychiatrists may contribute to the high incidence of medication errors and ADEs among psychiatric inpatients in Japan. Psychiatrists should be cautious in prescribing antipsychotics or unfamiliar medications for physical problems in their psychiatric patients, and should monitor patients after medication administration.

Relaxin-3 is a neuropeptide belonging to the relaxin/insulin superfamily. Studies using rodents have revealed that relaxin-3 is predominantly expressed in neurons in the nucleus incertus (NI) of the pons, the axons of which project to forebrain regions including the hypothalamus. There is evidence that relaxin-3 is involved in several functions, including food intake and stress responses. In the present study, we generated relaxin-3 gene knockout (KO) mice and examined them using a range of behavioral tests of sensory/motor functions and emotion-related behaviors. The results revealed that relaxin-3 KO mice exhibited normal growth and appearance, and were generally indistinguishable from wild genotype littermates. There was no difference in bodyweight among genotypes until at least 28 weeks after birth. In addition, there were no significant differences between wild-type and KO mice in locomotor activity, social interaction, hot plate test performance, fear conditioning, depression-like behavior, and Y-maze test performance. However, in the elevated plus maze test, KO mice exhibited a robust increase in the tendency to enter open arms, although they exhibited normal performance in a light/dark transition test and showed no difference from wild-type mice in the time spent in central area in the open field test. On the other hand, a significant increase in the acoustic startle response was observed in KO mice. These results indicate that relaxin-3 is slightly involved in the anxiety-related behavior.

Non-human primate behaviors have a special value for the neurobiological study of the development of higher cognitive functions of humans, because of the near evolutional relation between two species. We surveyed results and futures of neurobiological studies of a retrieval task, a learning-set and a self-injurious behavior expressed by non-human primates. On the retrieval task that is related to the development of inhibitory control, it was revealed a hierarchical ordering of inhibitory control processes in which the distinct neuronal circuits were involved. On the learning-set that is related to the development of abstract thinking, neural circuits for the individual learning dramatically changed from an automatic process to a cognitive process depending on the learning-set formation. The self-injurious behavior is expressed during early normal development in humans, and no other animals but non-human primates express it without administration of drugs. For that behavior, probable change in interactions of multiple monoaminergic systems was suggested as its underlying causes. Further studies on development of higher cognitive functions using non-human primates could be required for understanding the nature of human cognition.