Neuropsychological Impairment and Its Association with Violence Risk in Japanese Forensic Psychiatric Patients: A Case-Control Study.

BACKGROUND: In Japan, the legislation directing treatment of offenders with psychiatric disorders was enacted in 2005. Neuropsychological impairment is highly related to functional outcomes in patients with psychiatric disorders, and several studies have suggested an association between neuropsychological impairment and violent behaviors. However, there have been no studies of neuropsychological impairment in forensic patients covered by the Japanese legislation. This study is designed to examine the neuropsychological characteristics of forensic patients in comparison to healthy controls and to assess the relationship between neuropsychological impairment and violence risk. METHODS: Seventy-one forensic patients with psychiatric disorders and 54 healthy controls (matched by age, gender, and education) were enrolled. The CogState Battery (CSB) consisting of eight cognitive domains, the Iowa Gambling Task (IGT) to test emotion-based decision making, and psychological measures of violence risk including psychopathy were used. RESULTS: Forensic patients exhibited poorer performances on all CSB subtests and the IGT than controls. For each group, partial correlational analyses indicated that poor IGT performance was related to psychopathy, especially antisocial behavior. In forensic patients, the CSB composite score was associated with risk factors for future violent behavior, including stress and noncompliance with remediation attempts. CONCLUSION: Forensic patients with psychiatric disorders exhibit a wide range of neuropsychological impairments, and these findings suggest that neuropsychological impairment may increase the risk of violent behavior. Therefore, the treatment of neuropsychological impairment in forensic patients with psychiatric disorders is necessary to improve functional outcomes as well as to prevent violence.

Enhanced carbonyl stress in a subpopulation of schizophrenia.

CONTEXT: Various factors are involved in the pathogenesis of schizophrenia. Accumulation of advanced glycation end products, including pentosidine, results from carbonyl stress, a state featuring an increase in reactive carbonyl compounds (RCOs) and their attendant protein modifications. Vitamin B(6) is known to detoxify RCOs, including advanced glycation end products. Glyoxalase I (GLO1) is one of the enzymes required for the cellular detoxification of RCOs. OBJECTIVES: To examine whether plasma levels of pentosidine and serum vitamin B(6) are altered in patients with schizophrenia and to evaluate the functionality of GLO1 variations linked to concomitant carbonyl stress. DESIGN: An observational biochemical and genetic analysis study. SETTING: Multiple centers in Japan. PARTICIPANTS: One hundred six individuals (45 schizophrenic patients and 61 control subjects) were recruited for biochemical measurements. Deep resequencing of GLO1 derived from peripheral blood or postmortem brain tissue was performed in 1761 patients with schizophrenia and 1921 control subjects. MAIN OUTCOME MEASURES: Pentosidine and vitamin B(6) concentrations were determined by high-performance liquid chromatographic assay. Protein expression and enzymatic activity were quantified in red blood cells and lymphoblastoid cells using Western blot and spectrophotometric techniques. RESULTS: We found that a subpopulation of individuals with schizophrenia exhibit high plasma pentosidine and low serum pyridoxal (vitamin B(6)) levels. We also detected genetic and functional alterations in GLO1. Marked reductions in enzymatic activity were associated with pentosidine accumulation and vitamin B(6) depletion, except in some healthy subjects. Most patients with schizophrenia who carried the genetic defects exhibited high pentosidine and low vitamin B(6) levels in contrast with control subjects with the genetic defects, suggesting the existence of compensatory mechanisms. CONCLUSIONS: Our findings suggest that GLO1 deficits and carbonyl stress are linked to the development of a certain subtype of schizophrenia. Elevated plasma pentosidine and concomitant low vitamin B(6) levels could be the most cogent and easily measurable biomarkers in schizophrenia and should be helpful for classifying heterogeneous types of schizophrenia on the basis of their biological causes.