Association of interleukin-6 with suicidal ideation in veterans: a longitudinal perspective.

Introduction: Studies showing associations between inflammation in suicide are typically cross-sectional. Present study investigated how cytokine levels track with suicidal ideation and severity longitudinally. Methods: Veterans with a diagnosis of major depressive disorder (MDD) with or without suicide attempt history (MDD/SA n = 38, MDD/NS n = 41) and non-psychiatric non-attempter controls (HC n = 33) were recruited, MDD/SA and HC groups were followed longitudinally at 3 months and 6 months. Blood plasma was collected and processed using Luminex Immunology Multiplex technology. Results: Significant differences in depression severity (BDI) and suicidal ideation severity (SSI) were observed across all groups at study entry, wherein MDD/SA group had the highest scores followed by MDD/NS and HC, respectively. Cytokines IL-1ß, IL-4, TNF-α, IFN-γ, and IL-6 were examined at study entry and longitudinally, with IL6 levels differing significantly across the groups (p = 0.0123) at study entry. Significant differences in changes in cytokine levels between depressed attempters and the control group were detected for IL-6 (interaction F1,91.77 = 5.58, p = 0.0203) and TNF-α (F1,101.73 = 4.69, p = 0.0327). However, only depressed attempters showed a significant change, in IL-6 and TNF-α levels, decreasing over time [IL-6: b = -0.04, 95% CI = (-0.08, -0.01), p = 0.0245 and TNF-α: b = -0.02, 95% CI = (-0.04, -0.01), p = 0.0196]. Although IL-6 levels were not predictive of suicidal ideation presence [OR = 1.34, 95% CI = (0.77, 2.33), p = 0.3067], IL-6 levels were significantly associated with suicidal ideation severity (b = 0.19, p = 0.0422). Discussion: IL-6 was not associated with presence of suicidal ideation. IL-6 however, was associated with severity of ideation, suggesting that IL-6 may be useful in clinical practice, as an objective marker of heightened suicide risk.

Neural correlates of impulsivity in bipolar disorder: A systematic review and clinical implications.

Impulsivity is a common feature of bipolar disorder (BD) with ramifications for functional impairment and premature mortality. This PRISMA-guided systematic review aims to integrate findings on the neurocircuitry associated with impulsivity in BD. We searched for functional neuroimaging studies that examined rapid-response impulsivity and choice impulsivity using the Go/No-Go Task, Stop-Signal Task, and Delay Discounting Task. Findings from 33 studies were synthesized with an emphasis on the effect of mood state of the sample and affective salience of the task. Results suggest trait-like brain activation abnormalities in regions implicated in impulsivity that persist across mood states. During rapid-response inhibition, BD exhibit under-activation of key frontal, insular, parietal, cingulate, and thalamic regions, but over-activation of these regions when the task involves emotional stimuli. Delay discounting tasks with functional neuroimaging in BD are lacking, but hyperactivity of orbitofrontal and striatal regions associated with reward hypersensitivity may be related to difficulty delaying gratification. We propose a working model of neurocircuitry dysfunction underlying behavioral impulsivity in BD. Clinical implications and future directions are discussed.

Pilot evaluation of horticultural therapy in improving overall wellness in veterans with history of suicidality.

OBJECTIVES: Novel approaches to mental health and suicide prevention are lacking. Converging evidence has shown the effectiveness of horticultural therapy (HT) in improving mental health symptoms, but whether it would reduce suicide risk and contributing risk factors is unknown. DESIGN: Using a cohort model, HT was delivered 3.5 h over four weekly, sessions administered by a registered horticultural therapist to veterans with history of suicide ideation or attempt who felt isolated and experienced ongoing environmental stressors with interest in learning new coping strategies. SETTING: HT delivery occurred in an urban garden, through a community partnership between the VA (Veterans Administration) and the New York Botanical Garden. Guided by principles of biophilia, participating veterans took part in nature walks, self-reflection and journaling, and planting activities. OUTCOME MEASURES: Stress, mood, pain, and social isolation levels were measured weekly pre-post HT sessions using thermometer scales, with concordant validity to validated clinical instruments. RESULTS: Of the 20 men and women with a history of suicide attempts/ideation, HT demonstrated immediate improvements after each session across all symptom domains in magnitude of reduction in stress, pain, mood, and loneliness. The effect sizes were in medium to large range (Cohen's d>.5). Additionally, a single HT session showed a sustained effect over subsequent 2-to-4 weeks as observed by the significantly decreased pre-session thermometer scores in subsequent weeks. Reductions in mood symptoms correlated with decline in suicidal ideation (rs = 0.63). CONCLUSION: HT intervention maybe a promising therapeutic modality for improving overall wellness in suicide prevention in at-risk veteran populations.

Effectiveness of Complementary and Integrative Approaches in Promoting Engagement and Overall Wellness Toward Suicide Prevention in Veterans.

Objective: Suicide is a major public health problem, specifically among U.S. veterans, who do not consistently engage in mental health services, often citing stigma as a barrier. Complementary and Integrative Health (CIH) interventions are promising alternatives in promoting patient engagement and further, they may play a critical role in transitioning people into mental health care. Toward this goal, the Resilience and Wellness Center (RWC) was developed to break through the stigma barrier by addressing risk factors of suicide through multimodal CIH interventions via cohort design, promoting social connectedness and accountability among participants. Design: This is a program evaluation study at a large urban VA medical center, where assessments were evaluated from pre- to post-program completion to determine the effectiveness of an intensive multimodal CIH 4-week group outpatient intervention for suicide prevention. Outcome measures: Primary outcomes measured included group connectedness, severity of depression and hopelessness symptoms, suicidal ideation, sleep quality, and diet. Secondary outcomes included measures of post-traumatic stress disorder (PTSD), generalized anxiety severity stress/coping skills, pain, and fatigue. Results: The RWC showed high participant engagement, with an 84%-95% attendance engagement rate depending on suicide risk history. Data from 15 cohorts (N = 126) demonstrate favorable outcomes associated with participation in this comprehensive program, as evidenced by a reduction in suicidal ideation, depression, and hopelessness, but not sleep quality and diet. In addition, in a subset of veterans with a history of suicidal ideation or attempt, significant improvements were noted in pain, PTSD/anxiety symptoms, and stress coping measures. Conclusions: The RWC shows that an intensive complement of CIH interventions is associated with a significant improvement with high veteran engagement. Findings from this program evaluation study can be used to aid health care systems and their providers in determining whether or not to utilize such multimodal CIH integrated interventions as an effective treatment for at-risk populations as a part of suicide prevention efforts.

The association of childhood trauma with sleep disturbances and risk of suicide in US veterans.

BACKGROUND: Sleep dysregulation is prevalent among veterans and is associated with increased risk of suicidal ideation and behaviors. A confluence of risk factors have been identified to date that contribute to increase risk for suicidal behavior. How these risk factors including childhood trauma, comorbid psychopathology, impulsivity, and hostility together with sleep disturbance contribute to suicide risk remains an open question. These factors have never been examined simultaneously in a unified mediation model, as investigated in the present study, to determine their relative contribution to suicide risk. METHODS: Veterans (N = 105) were recruited across 3-groups, including Major Depressive Disorder (MDD) with/without a history of a suicide attempt (n = 35 and n = 37, respectively), and non-psychiatric controls, who had no history of mental illness or suicidal behavior (n = 33). The participants were assessed using validated self-report assessments with in-depth phenotyping for relevant risk factors associated with suicidal behavior including childhood adversity, depression severity, impulsivity, hostility, and sleep quality. These factors were included in mediation models using path analysis. RESULTS: Across all subjects including those with MDD and non-psychiatric controls, mediation analysis showed that higher levels of childhood trauma had an indirect effect on poor sleep quality (p = 0.001). This effect was orthogonal, being independently mediated by both MDD psychopathology (p = 0.003), and higher traits of impulsivity (p = 0.001) and hostility (p = 0.015). Amongst MDD veterans, childhood trauma was directly associated with increased suicide risk (p = 0.034), irrespective of their severity of depression, or their degree of hostility and impulsivity. LIMITATIONS: include use of self-report data, and the inability to establish causal inferences with cross-sectional design. CONCLUSION: Childhood adversity as a significant pre-deployment risk factor for disturbed sleep and elevated suicide risk, potentially important for incorporation in clinical practice for suicide.