Pyridoxamine: A novel treatment for schizophrenia with enhanced carbonyl stress.

AIM: The aim of this clinical trial was to obtain proof of concept for high-dose pyridoxamine as a novel treatment for schizophrenia with enhanced carbonyl stress. METHODS: Ten Japanese schizophrenia patients with high plasma pentosidine, which is a representative biomarker of enhanced carbonyl stress, were recruited in a 24-week, open trial in which high-dose pyridoxamine (ranging from 1200 to 2400 mg/day) was administered using a conventional antipsychotic regimen. Main outcomes were the total change in Positive and Negative Syndrome Scale score and the Brief Psychiatric Rating Scale score from baseline to end of treatment at week 24 (or at withdrawal). RESULTS: Decreased plasma pentosidine levels were observed in eight patients. Two patients showed marked improvement in their psychological symptoms. A patient who harbors a frameshift mutation in the Glyoxalase 1 gene also showed considerable reduction in psychosis accompanied with a moderate decrease in plasma pentosidine levels. A reduction of greater than 20% in the assessment scale of drug-induced Parkinsonism occurred in four patients. Although there was no severe suicide-related ideation or behavior, Wernicke's encephalopathy-like adverse drug reactions occurred in two patients and were completely suppressed by thiamine supplementation. CONCLUSION: High-dose pyridoxamine add-on treatment was, in part, effective for a subpopulation of schizophrenia patients with enhanced carbonyl stress. Further randomized, placebo-controlled trials with careful monitoring will be required to validate the efficacy of high-dose pyridoxamine for these patients.

Pathways from life-historical events and borderline personality disorder to symptomatic disorders among suicidal psychiatric patients: A study of structural equation modeling.

AIMS: Suicidal behavior (SB) is a major mental health problem. The research has identified many factors related to SB, such as problems in the developmental period and psychiatric and personality disorders. However, the interrelation of these factors has not been clearly delineated. METHODS: The subjects were 155 patients consecutively admitted with SB to a psychiatric center in Tokyo. Structured interviews, including the Structured Clinical Interview for DSM-IV (SCID)-I and SCID-II, were conducted to determine characteristics of the SB-related factors. To illustrate their interrelation, this study applied the technique of structural equation modeling. The latent constructs of life-historical events, borderline personality disorder (BPD) features and three symptomatic disorders (depression, anxiety disorders and substance dependence) were aligned in the chronological order of their manifestation, and connected one another within the model. Indicator variables of life-historical events were maltreatment in the developmental period and early onset of problematic behaviors. Indicators of BPD features and symptomatic disorders included the scales composed of the items in the SCID-I and II. RESULTS: The constructed model with favorable goodness-of-fit indices confirmed that BPD features had a mediating role in which they were influenced by life-historical events, and exerted an influence on the symptomatic disorders. Outside the BPD-mediating paths, the model suggested three clinically interpretable links between life-historical events and symptomatic disorders. CONCLUSIONS: The model of this study demonstrated the pathways from life-historical events and BPD to symptomatic disorders, and indicated a generating process of psychiatric comorbidity among suicidal patients. The wide-range view this study portrayed has important clinical implications, and deserves further substantiation by future studies.

Post-hospitalization course and predictive signs of suicidal behavior of suicidal patients admitted to a psychiatric hospital: a 2-year prospective follow-up study.

BACKGROUND: Suicidal patients admitted to a psychiatric hospital are considered to be at risk of suicidal behavior (SB) and suicide. The present study aimed to seek predictors of SB recurrence of the high-risk patients by examining their post-hospitalization course. METHOD: The design was 2-year prospective follow-up study of patients consecutively admitted with SB to a psychiatric center in Tokyo. The DSM-IV diagnoses and SB-related features of subjects were determined in structured interviews. Subsequently, the subjects underwent a series of follow-up assessments at 6-month intervals. The assessment included inquiries into SB recurrence, its accompanying suicidal intent (SI) and SF-8 health survey. Analyses of serial change over time in the follow-up data and Cox proportional hazards regression analyses of SB recurrence were performed. RESULTS: 106 patients participated in this study. The dropout rate during the follow-up was 9%. Within 2 years, incidences of SB as a whole, SB with certain SI (suicide attempt) and suicide were 67% (95% CI 58 - 75%), 38% (95% CI 29 - 47%) and 6% (95% CI 3 - 12%), respectively. Younger age, number of lifetime SBs and maltreatment in the developmental period were predictive of SB as a whole, and younger age and hopelessness prior to index admission were predictive of suicide attempt. Regarding diagnostic variables, anxiety disorders and personality disorders appeared to have predictive value for SB. Additionally, poor physical health assessed during the follow-up was indicated as a possible short-term predictor of SB recurrence. CONCLUSIONS: This study demonstrated a high incidence of SB and suicide and possible predictors of SB recurrence in the post-hospitalization period of psychiatric suicidal patients. Specialized interventions should be developed to reduce the suicide risk of this patient population.

Psychiatric disorders and clinical correlates of suicidal patients admitted to a psychiatric hospital in Tokyo.

BACKGROUND: Patients admitted to a psychiatric hospital with suicidal behavior (SB) are considered to be especially at high risk of suicide. However, the number of studies that have addressed this patient population remains insufficient compared to that of studies on suicidal patients in emergency or medical settings. The purpose of this study is to seek features of a sample of newly admitted suicidal psychiatric patients in a metropolitan area of Japan. METHOD: 155 suicidal patients consecutively admitted to a large psychiatric center during a 20-month period, admission styles of whom were mostly involuntary, were assessed using Structured Clinical Interviews for DSM-IV Axis I and II Disorders (SCID-I CV and SCID-II) and SB-related psychiatric measures. Associations of the psychiatric diagnoses and SB-related characteristics with gender and age were examined. RESULTS: The common DSM-IV axis I diagnoses were affective disorders 62%, anxiety disorders 56% and substance-related disorders 38%. 56% of the subjects were diagnosed as having borderline PD, and 87% of them, at least one type of personality disorder (PD). SB methods used prior to admission were self-cutting 41%, overdosing 32%, self-strangulation 15%, jumping from a height 12% and attempting traffic death 10%, the first two of which were frequent among young females. The median (range) of the total number of SBs in the lifetime history was 7 (1-141). Severity of depressive symptomatology, suicidal intent and other symptoms, proportions of the subjects who reported SB-preceding life events and life problems, and childhood and adolescent abuse were comparable to those of the previous studies conducted in medical or emergency service settings. Gender and age-relevant life-problems and life events were identified. CONCLUSIONS: Features of the studied sample were the high prevalence of affective disorders, anxiety disorders and borderline PD, a variety of SB methods used prior to admission and frequent SB repetition in the lifetime history. Gender and age appeared to have an influence on SB method selection and SB-preceding processes. The findings have important implications for assessment and treatment of psychiatric suicidal patients.

[Psychiatric and personality disorders and clinical characteristics of admitted suicidal patients: data from Matsuzawa Suicidal Behavior Study].

Psychiatric patients who have shown suicidal behavior (SB) are belived to be at a particularly high risk of suicide. However, the number of studies that have sought ways to prevent suicide in this patient population is limited. The present study investigated the diagnosis and SB-related characteristics of psychiatric inpatients showing suicidal behavior prior to admission. One-hundred and fifty-seven eligible subjects were recruited from patients consecutively admitted to a large psychiatric facility during a 20-month period in 2006 and 2007, and underwent extensive research interviews. Percentages of diagnoses based on the Structured Clinical Interview for DSM-IV, Clinician Version (SCID-I, CV) in this series were: affective disorders, 62%; anxiety disorders, 55%; substance use disorders, 38%; psychotic disorders, 27%; and eating disorders, 10%. Eighty-seven percent of the subjects were diagnosed as having some type of personality disorder (PD) in the SCID-II interview. Borderline PD was diagnosed in 56% of the subjects, making it the most frequent type of PD in this series. Frequent SB in these subjects involved: self-cutting, 40%; overdosing, 32%; self-strangulation, 14%; and jumping, 11%. Step-wise logistic regression analyses were conducted to examine the association of dichotomized SB-related clinical characteristics with diagnostic categories (affective disorders, psychotic disorders, substance use disorders, anxiety disorders, and cluster A, B and C PDs). The analysis demonstrated that three diagnostic categories were dominant in the association with clinical characteristics. Cluster B PD was associated with a history of overdosing, greater aggressiveness, interpersonal and life-situational life events, and childhood maltreatment (physical abuse and neglect). Anxiety disorders were related to histories of overdosing, dissociative symptoms in SB, excessive worry concerning life problems, and childhood neglect. Affective disorders were mainly associated with the characteristics of SB or SB-related symptoms: severe depressive symptoms and hopelessness, potentially fatal SB before admission such as self-strangulation, and dissociative symptoms in SB, though they did not show a significant relationship with pre-SB characteristics such as life events or childhood maltreatment. These findings will be helpful to develop treatment guidelines, SB-prevention strategies, and future research regarding suicidal psychiatric patients.

Motivation factors for suicidal behavior and their clinical relevance in admitted psychiatric patients.

BACKGROUND: Suicidal behavior (SB) is a major, worldwide health concern. To date there is limited understanding of the associated motivational aspects which accompany this self-initiated conduct. AIMS: To develop a method for identifying motivational features associated with SB by studying admitted psychiatric patients, and to examine their clinical relevance. METHODS: By performing a factor analytic study using data obtained from a patient sample exhibiting high suicidality and a variety of SB methods, Motivations for SB Scale (MSBS) was constructed to measure the features. Data included assessments of DSM-IV psychiatric and personality disorders, suicide intent, depressive symptomatology, overt aggression, recent life events (RLEs) and methods of SB, collated from structured interviews. Association of identified features with clinical variables was examined by correlation analyses and MANCOVA. RESULTS: Factor analyses elicited a 4-factor solution composed of Interpersonal-testing (IT), Interpersonal-change (IC), Self-renunciation (SR) and Self-sustenance (SS). These factors were classified according to two distinctions, namely interpersonal vs. intra-personal directedness, and the level of assumed influence by SB or the relationship to prevailing emotions. Analyses revealed meaningful links between patient features and clinical variables. Interpersonal-motivations (IT and IC) were associated with overt aggression, low suicidality and RLE discord or conflict, while SR was associated with depression, high suicidality and RLE separation or death. Borderline personality disorder showed association with IC and SS. When self-strangulation was set as a reference SB method, self-cutting and overdose-taking were linked to IT and SS, respectively. CONCLUSIONS: The factors extracted in this study largely corresponded to factors from previous studies, implying that they may be useful in a wider clinical context. The association of these features with SB-related factors suggests that they constitute an integral part of the process leading to SB. These results provide a base for further research into clinical strategies for patient management and therapy.