Roles of serum fibrinogen α chain-derived peptides in Alzheimer's disease.

OBJECTIVE: To find a blood biomarker and disease-related peptides in Alzheimer's disease (AD), we comprehensively detected serum peptides. METHODS: Ion intensity of serum peptides from 62 AD patients and 82 control subjects was measured by mass spectrometry. RESULTS: A total of 157 peptides were detected from 30 AD patients and 30 healthy control (HC) subjects. Sixty out of the 157 peptide profiles discriminated between the AD and HC groups. Sixteen out of the 60 peptides were identified, 10 out of which were fragments of a fibrinogen α chain (FIBA). Among the 10 peptides, four and six peptides were derived from fibrinopeptide A (FPA, Aα1-16) and the C-terminal region of the αC-domain (αCDC, Aα557-610), respectively. The profile of 10 FIBA-derived peptides combined with age discriminated between the two groups with an area under the receiver operating characteristic curve (AUROC) of 0.940. Validation of this model using a testing set of 32 AD patients and 19 HC subjects showed an AUROC of 0.717, sensitivity of 65.6%, and specificity of 73.7% by a cutoff value of 0.56420. Another value, 0.04029, showed sensitivity of 96.9%, suggesting that subjects with values less than 0.04029 rarely possess AD. FPA and αCDC showed increased ion intensity in the AD group compared with the HC group (p < 0.05). CONCLUSIONS: The profile of 10 FIBA-derived peptides combined with age would be a candidate biomarker for AD, which facilitates screening of the disease. The significant release of FPA and αCDC may be involved in the aberrant coagulation that leads to vascular damage in AD.

Exploring the Objective Signs of Imminent Suicide Risk in Psychiatric In-patients.

Objective: This study retrospectively explores the objective signs of imminent suicide risk in psychiatric in-patients. Design: The study analysed the diagnostic and nursing records of a psychiatric hospital that covered the last 14 days before the suicide attempts of 18 people, who, between March 2008 and July 2019, were found to have died by suicide during their hospital stay. Methods: Three professionals used a fishbone diagram to separately identify the factors that led to each person's suicide, the objective signs that indicated imminent suicide risk, possible preventive strategies, and other observations. They compared their findings and used the KJ method (Kawakita Jiro Method) to categorise the items on which they all agreed. Results: Objective signs of imminent suicide risk were condensed into five categories: 'signs emanating from the patient', 'signs gleaned through engagement', 'signs from response to treatment', 'signs associated with reports from the family', and 'signs inferred from multiple sources of information'. Five categories describing issues with the way in which the hospital staff handled information were extracted, namely 'omission in diagnostic records during admission', 'omission in conference records', 'communication lapse during transfer', 'need for integrated information', and 'systemic issues'. Conclusions: The findings offer insights on assessing suicide risk and preventing suicide.

Predictors of response to electroconvulsive therapy obtained using the three-factor structure of the Montgomery and Asberg Depression Rating Scale for treatment-resistant depressed patients.

OBJECTIVE: Electroconvulsive therapy (ECT) is one of the most effective treatments for refractory major depressive disorder (MDD). Although studies have examined different predictors of a positive response to ECT, predictors based on symptoms listed on a depression rating scale have not been studied. METHODS: This study included 24 Japanese patients who fulfilled the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria for MDD or bipolar disorder with current major depressive episode. All subjects had a score of 21 or higher on the Montgomery and Asberg Depression Rating Scale (MADRS). The 3-factor model of MADRS was used for analysis: factor 1 (dysphoria) was defined by 3 items, factor 2 (retardation) was defined by 4 items, and factor 3 (vegetative symptoms) was defined by 3 items. Electroconvulsive therapy was performed 2 times a week for a total of 6 sessions using the Thymatron System IV device (Somatics, Inc., Lake Bluff, Ill) with the brief-pulse technique. A clinical response was defined as a 50% or greater decrease on the pretreatment total MADRS score. RESULTS: The mean factor 1 score of responders (n = 17) at pretreatment was significantly higher than that of the nonresponders (n = 7). Furthermore, a significant difference in mean factor 3 scores between responders and nonresponders was observed 1 week after the 6 ECT sessions were complete, indicating a lag in response time. No significant differences were observed in age, number of previous episodes, and duration of current episodes between the responders and nonresponders. CONCLUSIONS: This study suggests that a high factor 1 MADRS score at pretreatment was a good predictor of response to ECT in patients with treatment-resistant MDD.

Symptom predictors of response to electroconvulsive therapy in older patients with treatment-resistant depression.

BACKGROUND: Electroconvulsive therapy (ECT) has been used for treatment-resistant depression. However, predictors of response to ECT have not been adequately studied using the Montgomery and Åsberg Depression Rating Scale, especially in older patients with treatment-resistant depression. METHODS: This study included 18 Japanese patients who fulfilled the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision criteria for a diagnosis of major depressive disorder or bipolar disorder with a current major depressive episode, and met the definition of treatment-resistant depression outlined by Thase and Rush, scoring ≥21 on the Montgomery and Åsberg Depression Rating Scale. The three-factor model of the Montgomery and Åsberg Depression Rating Scale was used for analysis. Factor 1 was defined by three items, factor 2 by four items, and factor 3 by three items, representing dysphoria, retardation, and vegetative symptoms, respectively. ECT was performed twice a week for a total of six sessions using a Thymatron System IV device with the brief pulse technique. Clinical responses were defined on the basis of a ≥50% decrease in total pretreatment Montgomery and Åsberg Depression Rating Scale scores. RESULTS: The mean pretreatment factor 2 score for responders (n = 7) was significantly lower than that for nonresponders (n = 11). Furthermore, a significant difference in mean factor 3 score between responders and nonresponders was observed one week after six sessions of ECT, indicating a time lag of response. No significant differences were observed for age, number of previous episodes, and duration of the current episode between responders and nonresponders. CONCLUSION: This study suggests that a low pretreatment factor 2 score is a good predictor of response to ECT in older patients with major depression.