Multiple serum biomarkers for predicting suicidal behaviours in depressive patients receiving pharmacotherapy.

BACKGROUND: Predictive values of multiple serum biomarkers for suicidal behaviours (SBs) have rarely been tested. This study sought to evaluate and develop a panel of multiple serum biomarkers for predicting SBs in outpatients receiving a 12-month pharmacotherapy programme for depressive disorders. METHODS: At baseline, 14 serum biomarkers and socio-demographic/clinical characteristics including previous suicidal attempt and present suicidal severity were evaluated in 1094 patients with depressive disorders without a bipolar diagnosis. Of these, 884 were followed for increased suicidal severity and fatal/non-fatal suicide attempt outcomes over a 12-month treatment period. Individual and combined effects of serum biomarkers on these two prospective SBs were estimated using logistic regression analysis after adjustment for relevant covariates. RESULTS: Increased suicidal severity and fatal/non-fatal suicide attempt during the 12-month pharmacotherapy were present in 155 (17.5%) and 38 (4.3%) participants, respectively. Combined cortisol, total cholesterol, and folate serum biomarkers predicted fatal/non-fatal suicide attempt, and these with interleukin-1 beta and homocysteine additionally predicted increased suicidal severity, with clear gradients robust to adjustment (p values < 0.001). CONCLUSIONS: Application of multiple serum biomarkers could considerably improve the predictability of SBs during the outpatient treatment of depressive disorders, potentially highlighting the need for more frequent monitoring and risk appraisal.

Investigating associations of childhood abuse and serum brain-derived neurotrophic factor levels with suicidal behaviours in patients with depressive disorders.

BACKGROUND: The role of childhood abuse and serum brain-derived neurotrophic factor (BDNF) levels in suicidal behaviour is controversial. AIMS: We aimed to investigate the individual and interactive effects of the childhood abuse and serum BDNF on suicidal behaviour before and after pharmacologic treatment in patients with depressive disorders. METHOD: At baseline, reported childhood emotional, physical and sexual abuse were ascertained and serum BDNF levels were measured in 1094 patients with depressive disorder, 884 of whom were followed during a 1-year period of stepwise pharmacotherapy. Suicidal behaviours evaluated at baseline were previous suicide attempt and baseline suicide severity, and suicidal behaviours evaluated at follow-up were increased suicide severity and fatal/non-fatal suicide attempt. Individual and interactive associations of any childhood abuse and serum BDNF levels with four types of suicidal behaviours were analysed using logistic regression models, after adjusting relevant covariates. RESULTS: Individual associations of childhood abuse were significant only with previous suicide attempt, and no significant individual associations were found for serum BDNF with any suicide outcome. However, the presence of both childhood abuse and lower serum BDNF levels was associated with the highest prevalence/incidence of all four suicidal behaviours, with significant interactions for baseline suicide severity and fatal/non-fatal suicide attempt during follow-up. CONCLUSIONS: Synergistic interactive effects of child abuse and serum BDNF levels on suicidal behaviours were found before and after pharmacologic treatment in patients with depressive disorders. Information combining childhood abuse and serum BDNF levels could improve predictions of suicidal behaviour in patients with depressive disorders.

Brain Derived Neurotrophic Factor Methylation and Long-term Outcomes after Stroke Interacting with Suicidal Ideation.

Objective: This study aimed to evaluate the unexplored relationship between BDNF methylation, long-term outcomes, and its interaction with suicidal ideation (SI), which is closely associated with both BDNF expression and stroke outcomes. Methods: A total of 278 stroke patients were assessed for BDNF methylation status and SI using suicide-related item in the Montgomery-Åsberg Depression Rating Scale at 2 weeks post-stroke. We investigated the incidence of composite cerebro-cardiovascular events (CCVEs) during an 8-14-year period after the initial stroke as long-term stroke outcome. We conducted Cox regression models adjusted for covariates to evaluate the association between BDNF methylation status and CCVEs, as well as its interaction with post-stroke SI at 2 weeks. Results: Higher methylation status of CpG 1, 3, and 5, but not the average value, predicted a greater number of composite CCVEs during 8-14 years following the stroke. The associations between a higher methylation status of CpGs 1, 3, 5, and 8, as well as the average BDNF methylation value, and a greater number of composite CCVEs, were prominent in patients who had post-stroke SI at 2 weeks. Notably, a significant interaction between methylation status and SI on composite CCVEs was observed only for CpG 8. Conclusion: The significant association between BDNF methylation and poor long-term stroke outcomes, particularly amplified in individuals who had post-stroke SI at 2 weeks, suggested that evaluating the biological marker status of BDNF methylation along with assessing SI during the acute phase of stroke can help predict long-term outcomes.

Impact of suicidality on delayed-onset post-traumatic stress disorder is modified by age: A two-year longitudinal study.

OBJECTIVES: This study aimed to investigate the relationship between early suicidality and post-traumatic stress disorder (PTSD) onset in patients with physical injuries, focusing on age as a modifying factor. METHODS: At baseline, 1014 patients were evaluated for suicidality, age divided into younger (<60 years) vs. older (≥60 years) groups, and potential covariates. PTSD was diagnosed at follow-up at 3, 6, 12, and 24 months, and then were categorized into early-onset (within the first six months after trauma) and delayed-onset (more than six months after trauma). Logistic regression models were used after adjusting for covariates. RESULTS: Presence of suicidality at baseline was significantly associated with delayed-onset PTSD in older but not younger patients with significant interaction terms, whereas it was significantly associated with early-onset PTSD across all age groups. CONCLUSION: Age-specific associations were found between suicidality and PTSD onset. The findings highlight the importance of early suicidality assessment, especially in older patients for ongoing monitoring and support, and underscore the critical need for early PTSD identification and intervention for all ages.

Moderating role of functioning level on the association between suicidal ideation and delayed-onset post-traumatic stress disorder.

OBJECTIVES: This study aimed to investigate the relationship between suicidal ideation at baseline and the development of post-traumatic stress disorder (PTSD) in individuals who have experienced physical injuries, with a specific focus on how this relationship is moderated by the patient's functioning level. METHODS: Participants were consecutively recruited from a trauma center and prospectively followed for two years. At baseline, suicidal ideation was assessed using the Brief Psychiatric Rating Scale, and functioning level was evaluated using the Social and Occupational Functioning Assessment Scale. During the follow-up, PTSD diagnosis was established using the Clinician-Administered PTSD Scale for DSM-5. Binary and multinomial logistic regression analyses were employed to examine the associations between suicidal ideation, functioning level, and PTSD. RESULTS: Of the 1014 participants analyzed, 114 (11.2%) developed PTSD, with early-onset observed in 79 (7.8%) and delayed-onset in 35 (3.5%) cases. Suicidal ideation at baseline was significantly associated with both early- and delayed-onset PTSD. Notably, higher functioning individuals with baseline suicidal ideation had an increased likelihood of developing delayed-onset PTSD, while this association was not significant in lower functioning individuals, with significant interaction terms. Additionally, suicidal ideation was a consistent predictor of early-onset PTSD across all functioning levels. CONCLUSION: The impact of baseline suicidal ideation on PTSD varies depending on the individual's functioning level, with higher functioning individuals being more vulnerable to delayed-onset PTSD. These findings underscore the importance of considering functional status in the assessment and intervention of PTSD following physical trauma.

Possible Link between Serotonin and Interleukin 18 on Suicidality in Patients with Acute Coronary Syndrome.

Objective: We investigated effects of serum serotonin and interleukin 18 levels on suicidal ideation (SI) at acute and chronic phases of acute coronary syndrome (ACS). Methods: Recent-onset 969 ACS patients were evaluated for serum serotonin and interleukin 18 levels; and SI by the "suicidal thoughts" item of the Montgomery-Åsberg Depression Rating Scale. After 1-year, 711 patients were re-evaluated for SI. Logistic regression models were used adjustment for potential covariates. Results: Associations between serum interleukin 18 and SI at both phases were significant only in the lower serotonin group. Conclusion: By evaluating serum serotonin and interleukin 18 levels, the clinical prediction of SI of ACS may be improved.

Serotonin modifies the impact of sleep disturbance on suicidality in patients with acute coronary syndrome.

Background: This study investigated the associations of sleep disturbance and serum serotonin levels with suicidal ideation, and evaluated the potential modifying effects of serotonin on these associations in patients with the acute coronary syndrome (ACS). Methods: In total, 969 ACS patients were recruited from a tertiary university hospital in Korea within 2 weeks of disease onset and evaluated in terms of sleep disturbance (using the Leeds Sleep Evaluation Questionnaire), serum serotonin levels, and suicidal ideation (using the "suicidal thoughts" item of the Montgomery-Åsberg Depression Rating Scale). Covariates included sociodemographics, depression, vascular risk factors, and disease severity. After 1 year, 711 patients were re-evaluated in terms of suicidal ideation. Logistic regression analysis was performed with adjustment for covariates. Results: Sleep disturbance was significantly associated with suicidal ideation at baseline and follow-up. Serum serotonin showed no such association but modified the association of sleep disturbance with suicidal ideation such that it was significant only in the lower serum serotonin group, with significant interaction terms obtained after adjustment for relevant covariates. Conclusion: Evaluating sleep disturbance and serum serotonin levels could improve the accuracy of clinical predictions of suicidal ideation in the acute and chronic phases of ACS.