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Association between irritability and suicidal ideation in three clinical trials of adults with major depressive disorder.

ABSTRACT: Irritability in pediatric samples is associated with higher rates of subsequent suicide-related outcomes. No study, to date, has evaluated the longitudinal association between irritability and suicidal ideation (SI) in adults with major depressive disorder (MDD). This report evaluated whether irritability is associated with SI at the same visit (i.e., concurrently) and whether early changes in irritability with antidepressant treatment predict subsequent levels of SI. Participants of Combining Medications to Enhance Depression Outcomes (CO-MED, n = 665), Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC, n = 296), and Suicide Assessment Methodology Study (SAMS, n = 266) were included. Repeated-measures mixed model analyses evaluated concurrent association throughout the trial between irritability (five-item irritability domain of Concise Associated Symptom Tracking scale) and SI (three-item suicidal thoughts factor of Concise Health Risk Tracking scale) after controlling for overall depression (excluding suicidality-related item), and predicted subsequent levels of SI (repeated observations from week-2-to-week-8) based on early (baseline-to-week-2) changes in irritability after controlling for early changes in overall depression. Higher irritability was associated with higher SI concurrently; estimates (standard error) were 0.18 (0.02, p < 0.0001), 0.64 (0.02, p < 0.0001), and 0.26 (0.04, p < 0.0001) in CO-MED, EMBARC, and SAMS respectively. Greater baseline-to-week-2 reductions in irritability predicted lower levels of subsequent SI; estimates (standard errors) were -0.08 (0.03, p = 0.023), -0.50 (0.05, p < 0.0001), and -0.12 (0.05, p = 0.024) in CO-MED, EMBARC, and SAMS, respectively. Controlling for anxiety or insomnia produced similar results. In conclusion, irritability and SI were consistently linked in adults with MDD. These findings support careful assessment of irritability in suicide risk assessment.

SUBMITTER: Jha MK

PROVIDER: S-EPMC7784964 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Major depressive disorder (MDD) and suicidal behavior have been associated with structural and functional changes in the brain. However, little is known regarding alterations of brain networks in MDD patients with suicidal ideation. We investigated whether or not MDD patients with suicidal ideation have different topological organizations of white matter networks compared with MDD patients without suicidal ideation. Participants consisted of 24 patients with MDD and suicidal ideation, 25 age- and gender-matched MDD patients without suicidal ideation and 31 healthy subjects. A network-based statistics (NBS) and a graph theoretical analysis were performed to assess differences in the inter-regional connectivity. Diffusion tensor imaging (DTI) was performed to assess topological changes according to suicidal ideation in MDD patients. The Scale for Suicide Ideation (SSI) and the Korean version of the Barrett Impulsiveness Scale (BIS) were used to assess the severity of suicidal ideation and impulsivity, respectively. Reduced structural connectivity in a characterized subnetwork was found in patients with MDD and suicidal ideation by utilizing NBS analysis. The subnetwork included the regions of the frontosubcortical circuits and the regions involved in executive function in the left hemisphere (rostral middle frontal, pallidum, superior parietal, frontal pole, caudate, putamen and thalamus). The graph theoretical analysis demonstrated that network measures of the left rostral middle frontal had a significant positive correlation with severity of SSI (r=0.59, P=0.02) and BIS (r=0.59, P=0.01). The total edge strength that was significantly associated with suicidal ideation did not differ between MDD patients without suicidal ideation and healthy subjects. Our findings suggest that the reduced frontosubcortical circuit of structural connectivity, which includes regions associated with executive function and impulsivity, appears to have a role in the emergence of suicidal ideation in MDD patients.

Project description:Importance:Suicidal ideation and suicide attempt (suicidality) are common in adolescence and a public health concern. Childhood depression is a key risk factor for later suicidality and often co-occurs with irritability. No study to date has examined the joint association of depressive mood and irritability during childhood with later suicidality. Objective:To investigate the association of childhood irritability and depressive/anxious mood profiles with adolescent suicidality. Design, Setting, and Participants:This population-based cohort study included 1430 participants in the Québec Longitudinal Study of Child Development. Participants underwent assessment yearly or bi-yearly (5 months to 17 years). Data were collected from March 16, 1998, through July 17, 2015. Exposures:Profiles defined by the joint developmental trajectories of irritability and depressive/anxious mood at 6 to 12 years of age. Main Outcomes and Measures:Self-reported past-year suicidality (ie, serious suicidal ideation or suicide attempt) at 13, 15, and 17 years of age. Irritability and depressive/anxious mood were assessed using teacher report 5 times from 6 to 12 years of age. Results:The study included 1430 participants (676 boys [47.3%] and 754 girls [52.7%]) followed up to 17 years of age. Group-based multitrajectory modeling identified the following profiles: combined no irritability and low depressive/anxious mood with low irritability and low depressive/anxious mood (831 [58.1%]; reference group), moderate irritability and low depressive/anxious mood (353 [24.7%]), high depressive/anxious mood only (94 [6.6%]), and high irritability and depressive/anxious mood (152 [10.6%]). Children with high irritability and high depressive/anxious mood reported higher rates of suicidality (25 of 152 [16.4%]) compared with the group with the lowest symptom levels (91 of 831 [11.0%]). In logistic regression analyses, the high irritability and depressive/anxious mood profile (odds ratio [OR], 2.22; 95% CI, 1.32-3.74; number needed to be exposed [NNE], 18) was associated with suicidality. To a lesser extent, the moderate irritability and low depressive/anxious mood profile was also associated with suicidality (OR, 1.51; 95% CI, 1.02-2.25; NNE?=?48). The high depressive/anxious mood only profile was not associated with later suicidality (OR, 0.96; 95% CI, 0.47-1.95; NNE?=?-320). The high irritability and depressive/anxious mood profile was associated with a higher suicidal risk compared with the depressive/anxious mood only profile (OR, 2.28; 95% CI, 1.02-5.15). Girls with the high irritability and high depressive/anxious mood profile had higher risk for suicidality (OR, 3.07; 95% CI, 1.54-6.12; NNE?=?5). Conclusions and Relevance:Children with high irritability and depressive/anxious mood and, to a lesser extent, with moderate irritability only had a higher suicidal risk during adolescence compared with children with low symptom levels. Early manifestation of chronic irritability during childhood, especially when combined with depressive/anxious mood, may be associated with an elevated risk for adolescent suicidality. The putatively causal role of irritability should be investigated.

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Association between irritability and suicidal ideation in three clinical trials of adults with major depressive disorder.

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