Occurrence and characteristics of suicidal ideation in psychiatrically healthy individuals based on ecological momentary assessment.

Decedents with no known mental disorder comprise 5-40% of suicides, suggesting that suicide ideation (SI) and behavior may occur in the psychiatrically healthy with important implications for suicide risk screening. Healthy Volunteers (HV) and patients with Major Depressive Disorder (MDD) provided 7 days of Ecological Momentary Assessment (EMA) data about SI and stressors. Longitudinal mixed effects logistic regression models compared HV and patient SI and stressors. Mixed effects linear regression models compared HVs' and patients' SI score change from the previous epoch's SI score when each stressor occurred. HVs (n = 42) reported less frequent (p < 0.001) and less intense SI (p < 0.003) than patients (n = 80), yet did endorse SI and/or SI-related items in 44% of EMA epochs, endorsing SI items in 25% of epochs with non-zero SI scores. For 7 of 8 stressors, patients reported stressors more often than HVs (all p < 0.001) responding to them with increased SI (0.0001 < p < 0.0472). HVs were relatively resilient to stressors, reporting SI increases only in response to neglect (p < 0.0147). Although SI and SAs are documented among psychiatrically healthy individuals, scientific attention to these observations has been scant. Real-time SI measurement showed that HVs' SI was less pronounced than MDD patients', but was endorsed, nonetheless. Patients were more likely to report stressors than HVs, perhaps due to greater sensitivity to the environment, and reported SI in response to stressors, which was less common in HVs. Both MDD patients and HVs most often manifested passive SI (viz, "decreased wish to live"). However, passive SI (viz, "desire for death"), may predict suicide, even absent SI per se (thinking about killing yourself). This study validates the utility of real-time SI assessment, showing that HVs endorse SI items in 11% of epochs, which implies that suicide risk screening focused on those with mental disorders may be too narrow an approach.

Acute Dissociation and Ketamine's Antidepressant and Anti-Suicidal Ideation Effects in a Midazolam-Controlled Trial.

OBJECTIVE: We sought to explore relationships of acute dissociative effects of intravenous ketamine with change in depression and suicidal ideation and with plasma metabolite levels in a randomized, midazolam-controlled trial. METHODS: Data from a completed trial in suicidal, depressed participants (n = 40) randomly assigned to ketamine was used to examine relationships between ketamine treatment-emergent dissociative and psychotomimetic symptoms with pre/post-infusion changes in suicidal ideation and depression severity. Nonparametric correlational statistics were used. These methods were also used to explore associations between dissociative or psychotomimetic symptoms and blood levels of ketamine and metabolites in a subset of participants (n = 28) who provided blood samples immediately post-infusion. RESULTS: Neither acute dissociative nor psychotomimetic effects of ketamine were associated with changes in suicidal ideation or depressive symptoms from pre- to post-infusion. Norketamine had a trend-level, moderate inverse correlation with dissociative symptoms on Day 1 post-injection (P = .064; P =.013 removing 1 outlier). Dehydronorketamine correlated with Clinician-Administered Dissociative States Scale scores at 40 minutes (P = .034), 230 minutes (P = .014), and Day 1 (P = .012). CONCLUSION: We did not find evidence that ketamine's acute, transient dissociative, or psychotomimetic effects are associated with its antidepressant or anti-suicidal ideation actions. The correlation of higher plasma norketamine with lower dissociative symptoms on Day 1 post-treatment suggests dissociation may be more an effect of the parent drug.

Plasma Phospholipid Polyunsaturated Fatty Acid Associations with Neurocognition.

Neurocognitive deficits are implicated in major depressive disorder (MDD) and suicidal behavior, and cognitive function may be affected by blood levels of polyunsaturated fatty acids (PUFAs). Neuroprotective functions have been described for omega-3 (n-3) PUFAs, while omega-6 (n-6) PUFAs exhibit broadly opposing activities. Both classes of PUFAs are linked to MDD and suicidal behavior. However, few studies have investigated the relationships between PUFAs and neurocognitive function with respect to MDD or suicidal behavior. Among participants with MDD (n = 45) and healthy volunteers (HV, n = 30) we assessed performance on tasks of attentional capacity and executive function and its relationship to plasma phospholipid PUFA levels, expressed as a percentage of total plasma phospholipids, for eicosapentaenoic acid (EPA%), docosahexaenoic acid (DHA%), and arachidonic acid (AA%). Regression models tested the correlations between PUFA levels and task performance in three groups: MDD with a history of suicide attempt (SA, n = 20), MDD with no attempts (NA, n = 25), and HV. Interaction testing indicated a significant positive correlation of EPA% with continuous performance test scores in the NA group (F = 4.883, df = 2,72, p = 0.01), a measure of sustained attention. The AA% correlated negatively with performance on two executive function tasks, object alternation (beta = -3.97, z-score = -2.67, p = 0.008) and the Wisconsin card sort (beta = 0.80, t-score = -2.16, df = 69, p = 0.035), after adjustment for group and age, with no group effects. Our findings suggest a role for PUFA imbalance in attentional functioning and executive performance; however, no MDD-specific effect was observed.

Antisuicidal effect of lithum in bipolar disorder: is there an age-specific effect?

OBJECTIVE: Our group reported previously a comparable overall antisuicidal effect of lithium and valproate in bipolar patients. We investigated factors associated with higher antisuicidal efficacy of lithium in older individuals. METHODS: The age-related antisuicidal effect of lithium and valproate was compared in ninety-four (n = 94) high-risk bipolar suicide attempters who participated in a 2.5-year randomized, double-blind trial. RESULTS: Age significantly moderated the effect of lithium vs. valproate on the risk of suicide event during the study (z = -1.98, p = 0.049). We found that those who were 42 years or older (above the 75th percentile), and on lithium had significantly lower risk of suicidal behavior than older patients on valproate (>42y) or younger (<42 y) patients on either medication (interaction HR = 0.09, 95%CI: 0.01-0.89, z = -2.07, p = 0.039). This difference in risk differences was not explained away by age-related differences in the proportion of participants with bipolar II disorder (Fisher's test p = 0.020) or higher lethality of past suicide attempts in younger participants (Wilcoxon test p = 0.024); neither was there any correlation with age in the longitudinally measured blood lithium levels (t = 1.04, df = 36, p = 0.307) or valproate levels (t = -0.50, df = 41, p = 0.621). LIMITATIONS: Besides the fact that this is a secondary analysis, a limitation is that the study is not powered to detect suicide deaths or suicide attempts. CONCLUSION: Bipolar patients randomized to lithium and older than 42 years had less suicidal behavior compared to same aged patients on valproate or younger patients (<42 y) on either medication. This effect was independent of clinical and sociodemographic characteristics.

Brain serotonin 1A receptor binding: relationship to peripheral blood DNA methylation, recent life stress and childhood adversity in unmedicated major depression.

BACKGROUND: Childhood and lifetime adversity may reduce brain serotonergic (5-HT) neurotransmission by epigenetic mechanisms. AIMS: We tested the relationships of childhood adversity and recent stress to serotonin 1A (5-HT1A) receptor genotype, DNA methylation of this gene in peripheral blood monocytes and in vivo 5-HT1A receptor binding potential (BPF) determined by positron emission tomography (PET) in 13 a priori brain regions, in participants with major depressive disorder (MDD) and healthy volunteers (controls). METHOD: Medication-free participants with MDD (n = 192: 110 female, 81 male, 1 other) and controls (n = 88: 48 female, 40 male) were interviewed about childhood adversity and recent stressors and genotyped for rs6295. DNA methylation was assayed at three upstream promoter sites (-1019, -1007, -681) of the 5-HT1A receptor gene. A subgroup (n = 119) had regional brain 5-HT1A receptor BPF quantified by PET. Multi-predictor models were used to test associations between diagnosis, recent stress, childhood adversity, genotype, methylation and BPF. RESULTS: Recent stress correlated positively with blood monocyte methylation at the -681 CpG site, adjusted for diagnosis, and had positive and region-specific correlations with 5-HT1A BPF in participants with MDD, but not in controls. In participants with MDD, but not in controls, methylation at the -1007 CpG site had positive and region-specific correlations with binding potential. Childhood adversity was not associated with methylation or BPF in participants with MDD. CONCLUSIONS: These findings support a model in which recent stress increases 5-HT1A receptor binding, via methylation of promoter sites, thus affecting MDD psychopathology.

Avoidant attachment transmission to offspring in families with a depressed parent.

BACKGROUND: Insecure attachment is associated with mental health morbidity. We explored associations between parent and offspring attachment style in a longitudinal study of families with a depressed parent. METHODS: Parents (N = 169) with a DSM-IV mood disorder and their adult offspring (N = 267), completed the Adult Attachment Questionnaire at one or more time points during up to 9.7 years of follow-up. Linear mixed effects models explored associations between parent and offspring anxious and avoidant attachment scores. Residualized models accounted for parent and offspring depression severity. RESULTS: Avoidant attachment scores were associated between parents and offspring with (p = .034) and without (p = .012) adjustment for baseline age and sex of parent and offspring. Depressed father-offspring relationships showed more avoidant attachment in offspring compared to depressed mother-offspring pairs (p = .010). After accounting for depression severity, parent average residualized avoidant attachment scores did not significantly correlate with those of offspring (unadjusted p = .052; adjusted p = .085), though the effect sizes did not change substantially, and 75 % of the correlation was retained. Parent-son relationships exhibited stronger avoidant attachment correlations compared to parent-daughter pairs (p = .048). LIMITATIONS: Small sub-sample of fathers, parent and offspring assessments not always completed at the same time, and use of a self-report attachment style instrument. CONCLUSIONS: Familial transmission of insecure avoidant attachment, a risk factor for negative mental health outcomes, merits research as a potential treatment target. In this preliminary study, its transmission to offspring seemed mostly independent of depression. Depressed fathers and their sons may deserve focus to reduce insecure avoidant attachment and improve clinical course.

Deconstructing resilience in patients at high risk for suicidal behavior.

BACKGROUND: Resilience represents coping abilities to overcome exposure to psychopathological risk. In the context of risk factors for suicidal behavior, it is unknown if this attribute is deficient in suicide attempters, how it relates to other measures of risk, and where it may overlap with other risk factors associated with suicidal behavior. METHODS: The present study examined the performance on the Connor-Davidson Resilience Scale (CD-RISC) in three groups of individuals with familial risk for both mood disorder and suicidal behavior, as well as a healthy comparison group. Other risk factors for suicidal behavior, such as depression severity, hopelessness, and lifetime impulsiveness were examined as well to determine if these mediated group differences in CD-RISC scores. RESULTS: CD-RISC scores differed between groups, with lowest scores in the past attempter group. However, CD-RISC scores were strongly correlated with other common risk factors for suicide attempt, including hopelessness, subjective depression, and reasons for living, which together explained 68 % of the CD-RISC variance. Group differences in CD-RISC scores were eliminated when the model included these covariates. LIMITATIONS: Sample sizes were modest, and depression severity was low overall and significantly higher in the past suicide attempter group. CONCLUSIONS: The CD-RISC has demonstrated utility for predicting risk for depression, but appears to overlap with other known risk factors for suicidal behavior, especially hopelessness and subjective depression. Though it encapsulates variance from multiple risk factors in a single scale, it may not provide additional predictive power above and beyond these other risk factors for suicidal behavior.

Ketamine vs midazolam: Mood improvement reduces suicidal ideation in depression.

OBJECTIVE: Studies demonstrate rapid antidepressant and anti-suicidal ideation effects of subanesthetic ketamine. The specific subcomponents of depression that are most closely tied to reduction of suicidal ideation with ketamine treatment are less explored. METHODS: Exploratory, post hoc analysis of data from a randomized clinical trial of ketamine vs midazolam in patients with major depressive disorder (MDD) and clinically significant suicidal ideation examined changes in factor analysis-derived symptom clusters from standard measures of depression (Hamilton Depression Rating Scale, HDRS; Beck Depression Inventory, BDI) and mood disturbance (Profile of Mood States, POMS), and their relationship to severity of suicidal ideation (Beck Scale for Suicidal Ideation; SSI). Ratings obtained before and one day after blinded intravenous infusion were decomposed into component factors or published subscales. Treatment effects on factors/subscales were compared between drugs, correlations with changes in suicidal ideation were tested, and stepwise regression was used to derive predictors of change in SSI. RESULTS: Factor scores for HDRS Psychic Depression, HDRS Anxiety, BDI Subjective Depression, POMS Depression and POMS Fatigue improved more with ketamine than midazolam. Stepwise regression showed across both drugs that improvement in HDRS Psychic Depression, POMS Depression, and HDRS Anxiety predicted 51.6% of the variance in reduction of suicidal ideation. LIMITATIONS: Secondary analysis of clinical trial data. CONCLUSIONS: Ketamine's rapid effects on suicidal ideation appear to be mostly a function of its effects on core mood and anxiety symptoms of MDD, with comparatively little contribution from neurovegetative symptoms with the potential exception of vigor/fatigue. TRIAL REGISTRATION: Data used in this secondary analysis came from ClinicalTrials.gov identifier: NCT01700829.

Effects of Ketamine Versus Midazolam on Neurocognition at 24 Hours in Depressed Patients With Suicidal Ideation.

Objective: Subanesthetic ketamine rapidly reduces depressive symptoms and suicidal ideation in some depressed patients. Its effects on neurocognitive functioning in such individuals with significant suicidal ideation is not well understood, even though certain neurocognitive deficits are associated with suicide behavior beyond clinical symptoms.Methods: In this study, depressed patients with clinically significant suicidal ideation (n = 78) underwent neuropsychological testing before and 1 day after double-blind treatment with intravenous ketamine (n = 39) or midazolam (n = 39). A subgroup randomized to midazolam whose ideation did not remit after initial infusion received open ketamine and additional neurocognitive testing a day after this treatment. The primary outcome was change in performance on this neurocognitive battery. The study was conducted between November 2012 and January 2017.Results: Blinded ketamine produced rapid improvement in suicidal ideation and mood in comparison to midazolam, as we had reported previously. Ketamine, relative to midazolam, was also associated with specific improvement in reaction time (Choice RT) and interference processing/cognitive control (computerized Stroop task)-the latter a measure that has been associated with past suicide attempt in depression. In midazolam nonremitters later treated with open ketamine and retested, reaction time and interference processing/cognitive control also improved relative to both of their prior assessments. Neurocognitive improvement, however, was not correlated with changes in depression, suicidal thinking, or general mood.Conclusions: Overall, ketamine was found to have a positive therapeutic effect on neurocognition 1 day after treatment on at least 1 measure associated with suicidal behavior in the context of depression. Results suggest additional independent therapeutic effects for ketamine in the treatment of depressed patients at risk for suicidal behavior.Trial Registration: ClinicalTrials.gov identifier: NCT01700829.

Age effects on clinical and neurocognitive risk factors for suicide attempt in depression - Findings from the AFSP lifespan study.

BACKGROUND: Studies of risk factors for suicidal behavior are typically restricted to narrow age ranges, making it difficult to determine if they have the same relevance or potency across the full adult lifespan. METHODS: This study examined selected clinical and neurocognitive risk factors for suicidal behavior - borderline personality traits, aggression, depressive rumination, memory performance, and language fluency- in a multi-site sample (N = 309, ages 16-80) of depressed patients with a recent (last 5 years) suicide attempt or no history of attempt, and demographically similar non-psychiatric controls. We examined cross-sectional age and attempter/non-attempter differences on these risk factors, and whether certain risk factors were more prominent discriminators of past suicide attempt earlier or later in the lifespan. Correlations with age were computed, and logistic regression was used to classify attempter status based on each risk factor and its interaction with age. RESULTS: Nearly all risk factors were negatively correlated with age. Borderline traits, aggression, memory, and category fluency each predicted attempter status (p < 0.05), but these effects were not different across ages. In contrast, the association between rumination and suicide attempt status differed across the lifespan, becoming a stronger discriminator of past suicidal behavior at older ages. LIMITATIONS: The cross-sectional design limits our developmental findings. CONCLUSIONS: Despite age-related changes in symptom severity or neurocognitive performance, key risk factors for suicidal behavior previously identified in studies with more restricted age-ranges are salient throughout the adult lifespan. In contrast, depressive rumination may be particularly salient in later life.

Examining the relationship between gray matter volume and a continuous measure of bipolarity in unmedicated unipolar and bipolar depression.

BACKGROUND: It has been argued that unipolar major depressive disorder (MDD) and bipolar disorder (BD) exist on a continuous spectrum, given their overlapping symptomatology and genetic diatheses. The Bipolarity Index (BI) is a scale that considers bipolarity as a continuous construct and was developed to assess confidence in bipolar diagnosis. Here we investigated whether BI scores correlate with gray matter volume (GMV) in a sample of unmedicated unipolar and bipolar depressed individuals. METHODS: 158 subjects (139 with MDD, 19 with BD) in a major depressive episode at time of scan were assigned BI scores. T1-weighted Magnetic Resonance Imaging scans were obtained and processed with Voxel-Based Morphometry using SPM12 (CAT12 toolbox) to assess GMV. Regression was performed at the voxel level to identify clusters of voxels whose GMV was associated with BI score, (p<0.001, family-wise error-corrected cluster-level p<0.05), with age, sex and total intracranial volume as covariates. RESULTS: GMV was inversely correlated with BI score in four clusters located in left lateral occipital cortex, bilateral angular gyri and right frontal pole. Clusters were no longer significant after controlling for diagnosis. GMV was not correlated with BI score within the MDD cohort alone. LIMITATIONS: Incomplete clinical data required use of a modified BI scale. CONCLUSION: BI scores were inversely correlated with GMV in unmedicated subjects with MDD and BD, but these correlations appeared driven by categorical diagnosis. Future work will examine other imaging modalities and focus on elements of the BI scale most likely to be related to brain structure and function.

Highly variable suicidal ideation: a phenotypic marker for stress induced suicide risk.

Suicidal behavior (SB) can be impulsive or methodical; violent or not; follow a stressor or no obvious precipitant. This study tested whether childhood trauma, affective lability, and aggressive and impulsive traits predicted greater SI variability. We also assessed whether affective lability, aggressive or impulsive traits explain childhood trauma's effects on SI variability and whether those with highly variable SI respond to stressful events with increases in SI. Finally, we assessed variable SI's trajectory over 2 years. Depressed participants (n = 51) had ecological momentary assessments (EMA) over 7 days at baseline, 3, 6, 12, 18, and 24 months. SI variability was assessed using the square Root of the Mean Square of Successive Deviations. Mixed Effects Models were fit as appropriate. Childhood trauma was associated with subsequent aggression. Physical abuse predicted both aggression and affective lability as well as SI variability, but not impulsivity. In two-predictor models, physical abuse's effect on SI variability was no longer significant, when controlling for the effect of higher aggression and impulsivity. Those with high SI variability exhibited greater increases in SI after stressors compared with those with less variability. We did not find that SI variability changed over time, suggesting it might be trait-like, at least over 2 years. Variable SI predisposes to marked SI increases after stressful events and may be a trait increasing risk for impulsive SB, at least over 2 years.

Psychosocial risk factors and outcomes associated with suicide attempts in childhood: A retrospective study.

OBJECTIVE: To examine factors differentiating individuals whose first suicide attempt was during childhood (ages 5-12 yrs) from those who first attempted suicide during adolescence (13-19 yrs) and during adulthood (≥20 yrs). METHOD: A sample of 418 participants (ages 18-64 yrs) with a mood disorder and ≥1 lifetime suicide attempt was divided into three groups according to age of first suicide attempt (childhood: N = 43, adolescent: N = 149, adulthood: N = 226) and compared on demographics, childhood adversity, parental psychopathology, comorbid lifetime axis I diagnoses, self-harm and characteristics of first attempt. RESULTS: Participants in the Childhood Attempt group were more likely to report childhood adversity, parental alcohol use disorder and subsequent suicide attempts than the two other groups. They were also more likely to have a depressed mother, non-suicidal self-injury (NSSI) during childhood and adolescence, lifetime PTSD and aggressive behavior than the Adulthood Attempt group. The Adolescent Attempt group had more childhood adversity, parental suicidal behavior, lifetime PTSD and NSSI during adolescence than the Adulthood Attempt group. The groups differed on methods of first attempt, and its lethality was related to age of attempt. CONCLUSIONS: Early adversity and parental psychopathology are particularly prominent in those who make childhood suicide attempts, suggesting that this group may represent a suicidal behavior subtype.

Ketamine metabolite pilot study in a suicidal depression trial.

Ketamine shows promise as a rapidly-acting treatment for depression and suicidal ideation, but side effects and abuse potential limit its use. Understanding its mechanism of action could help develop analogous but safer drugs. This post hoc study explored relationships of ketamine and metabolites, including hydroxynorketamine enantiomers, (2S,6S)- and (2R,6R)-HNK, to clinical response in a subgroup from a published trial in suicidal depression. Depressed adults with clinically significant suicidal ideation were randomized to double-blind infusion of sub-anesthetic ketamine or midazolam. Ketamine and metabolites were measured after infusion (N = 53). Plasma (2R,6R)-HNK was associated with change (higher levels correlated with less clinical improvement) from baseline to 24 h post-infusion of depression (HDRS-24: Spearman r = 0.37, p = 0.009) and suicidal thoughts (SSI: Spearman r = 0.29, p = 0.041). There were similar correlations with weekly follow-up clinical rating scores for both HNK enantiomers and dehydronorketamine (DHNK). Ketamine and norketamine were not associated with change in depression or suicidal ideation (unadjusted p > 0.28).

The impact of cognitive reserve on neurocognitive performance in Major Depressive Disorder.

Cognitive reserve may mitigate the degree of cognitive deficit observed in Major Depressive Disorder (MDD), confounding attempts to fully characterize the nature of these deficits. In this study, cognitive reserve was examined as a potential moderator of neurocognitive deficits in MDD. Unmedicated, currently depressed patients with MDD (n = 269), and healthy volunteers (n = 143) were compared on measures assessing psychomotor speed, interference processing, verbal memory, visual memory, and executive functioning. Moderating effects of education level and estimated intelligence level were examined as interactions, along with age, in a regression model for each test. Differences between patients and non-patients were found with most measures, and sustained in regression models as main effects. However, the interaction of estimated intelligence and patient status was significant for processing speed, verbal memory, visual memory, and executive functioning, with patient/non-patient differences diminishing with higher estimated intelligence. Neither estimated intelligence nor education level impacted interference processing differences, which were reduced with increasing age. Better intellectual ability moderates the effect of MDD on neurocognitive test performance. This effect may confound attempts to characterize these deficits in higher functioning samples. More challenging tasks may be needed, given the potential predictive value of neurocognition for differential therapeutic and clinical outcomes.

The lack of meaningful association between depression severity measures and neurocognitive performance.

BACKGROUND: Neurocognitive deficits are common in depression, but most prior studies have not found strong associations between standard measures of symptom severity and the extent of these neurocognitive deficits. Diagnostic heterogeneity, or the lack of specific questions about neurocognition in these measures, may be undermining these associations. METHOD: Neuropsychological performance was assessed via 10 tasks in a sample of 262 unmedicated patients with Major Depressive Disorder (MDD) and compared to that in healthy volunteers (n = 140), then correlated with (1) standard measures of depression severity including the Hamilton Depression Rating Scale and Beck Depression Inventory, (2) previously established, factor-analytically derived symptom factors that characterize the heterogeneity of these scales, and (3) a separate measure of cognitive complaint (Cognitive Failures Questionnaire) that was included to address the absence of specific questions about cognition in standard rating scales. RESULTS: Neurocognitive performance in these unmedicated MDD patients was not significantly associated with either total scores on the depression severity measures, any of their derived symptom factors, or the degree of subjective cognitive complaint - which itself was most strongly associated with mood disturbance. LIMITATIONS: Depressed patients with the most prominent neurovegetative symptoms may be underrepresented in this sample. CONCLUSIONS: Neurocognitive deficits were only weakly associated with standard depression symptom ratings, and not captured by self-report ratings of cognitive complaint. Neurocognitive deficits appear to be a separate symptom dimension that cannot be inferred from overall depression severity and require their own assessment, given that they have prognostic value for functional outcomes, suicide risk, and differential therapeutics.

Attempted suicide and oxytocin-related gene polymorphisms.

BACKGROUND: Oxytocin may moderate prosocial behaviors, but has also been implicated in negative mental health outcomes. A single-nucleotide polymorphism (SNP) of the oxytocin receptor gene (OXTR), rs53576, and a SNP of the CD38 gene, which regulates oxytocin secretion, rs3796863, have been associated with depression and suicidal ideation. METHODS: We conducted an exploratory study investigating the relationship of these two SNPs to history of suicide attempt. Secondary analyses explored relationships of genotype with sex, diagnosis, history of abuse, depression, suicidal ideation, and attachment and personality traits. Subjects were depressed adults with DSM-IV major depressive disorder (MDD; n = 161) or bipolar disorder (BD; n = 75). RESULTS: The A allele of rs53576 was associated with suicide attempt history. A differential effect of rs3796863 genotype on suicide attempt risk was found by diagnosis. In the BD sample, CC and AC genotypes were associated with higher odds of suicide attempt compared to AA, while in the MDD sample, AC subjects were more likely than CC subjects to have made an attempt. LIMITATIONS: Our assessment of social sensitivity was limited to measures of attachment style and abuse history and did not differentiate between types of abuse. Plasma oxytocin was not measured. CONCLUSIONS: These findings add to evidence for the involvement of oxytocin in suicide attempts and identify a potential biomarker for differentiating depressed attempters from non-attempters.

Effects of anxiety on suicidal ideation: exploratory analysis of a paroxetine versus bupropion randomized trial.

It is unclear whether anxiety increases or decreases suicidal risk. This may contribute to the lack of guidance on which antidepressant medications are best for suicidal depressed patients who present with high anxiety. This study explored whether anxiety predicts suicidal ideation in depressed individuals treated with paroxetine or bupropion. An 8-week double-blind trial comparing controlled-release paroxetine (N=36) versus extended-release bupropion (N=38) for effect on suicidal ideation and behavior in depressed patients with suicidal ideation, past attempt, or both found an advantage for paroxetine, but anxiety effects were not investigated. This secondary analysis explored the relationship, measured at baseline and weekly, of anxiety with suicidal ideation. Anxiety severity measured weekly correlated with suicidal ideation severity irrespective of treatment (P=0.012). Patients with high baseline anxiety showed a trend toward faster reduction of suicidal ideation with paroxetine compared with bupropion treatment (standard P=0.047; bootstrap P=0.077). The latter finding, if confirmed in larger samples, could enhance choice of antidepressant medication for suicidal, depressed patients presenting with high levels of anxiety.