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Neuroimaging-informed phenotypes of suicidal behavior: a family history of suicide and the use of a violent suicidal means.

ABSTRACT: The identification of brain markers of suicidal risk is highly expected. However, neuroimaging studies have yielded mixed results, possibly due to phenotypic heterogeneity. In the present study, we addressed this issue using structural brain imaging. First, two independent samples of suicide attempters (n?=?17 in Montreal, 32 in Jena), patient controls (n?=?26/34), and healthy controls (n?=?66/34) were scanned with magnetic resonance imaging. Groups were compared with FSL. We then reviewed the literature and run a GingerALE meta-analysis of 12 structural imaging studies comparing suicide attempters and patient controls with whole-brain analyses (n?=?693). Finally, we explored the potential contribution of two variables previously associated with biological/cognitive deficits: a family history of suicide (FHoS), and the use of a violent suicidal means (VSM). Here, we added two groups of healthy first-degree biological relatives of suicide victims and depressed patients (n?=?32). When comparing all suicide attempters and controls, very limited between-group differences were found in the two samples, and none in the meta-analysis. In contrast, a FHoS was associated with reduced volumes in bilateral temporal regions, right dorsolateral prefrontal cortex, and left putamen, several of these differences being observed across groups. VSM was associated with increased bilateral caudate (and left putamen) volumes. Some morphometric variations in cortico-subcortical networks may therefore be endophenotypes increasing the suicidal vulnerability, while others (notably in striatum) may modulate action selection. These results therefore confirm at the neural level two phenotypes at high lethal risk with a strong biological background, and uncover motives of heterogeneous findings in neuroimaging studies of suicidal behavior.

SUBMITTER: Jollant F

PROVIDER: S-EPMC6008434 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Neuroimaging-informed phenotypes of suicidal behavior: a family history of suicide and the use of a violent suicidal means.

Jollant Fabrice F Wagner Gerd G Richard-Devantoy Stéphane S Köhler Stefanie S Bär Karl-Jürgen KJ Turecki Gustavo G Pereira Fabricio F

Translational psychiatry 20180619 1

The identification of brain markers of suicidal risk is highly expected. However, neuroimaging studies have yielded mixed results, possibly due to phenotypic heterogeneity. In the present study, we addressed this issue using structural brain imaging. First, two independent samples of suicide attempters (n = 17 in Montreal, 32 in Jena), patient controls (n = 26/34), and healthy controls (n = 66/34) were scanned with magnetic resonance imaging. Groups were compared with FSL. We then reviewed the l ...[more]

PMID: 29921964

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Project description:IntroductionSeveral studies demonstrated that the hypothalamic-pituitary-adrenal (HPA) axis is dysregulated in suicide attempters. Prospective studies found that people with an abnormal response at the dexamethasone suppression test (DST) are more likely to commit suicide. However, whether DST may predict suicide attempts remains less clear. A possible strategy to address this question is to consider the suicide attempt lethality.Objectives(1) To compare the pre- and post-DST cortisol levels in serious/violent suicide attempters and in non-serious/non-violent suicide attempters, and (2) to investigate whether cortisol level can predict new suicide attempts or their lethality.MethodsThe study included 70 recent suicide attempters (25 with a serious or violent attempt) who were followed for two years. Three saliva samples for cortisol measurement were obtained at 8a.m., 3p.m., and 9p.m. before the DST (pre-DST). Then, at 11 p.m., 1 mg of dexamethasone was given orally. The following day (post-DST), three saliva samples were collected at the same hours as before. The post-DST-pre-DST salivary cortisol Δ index was calculated for each collection time. The Risk-Rescue Ratio Scale (RRRS) and the Suicidal Intent Scale (SIS) were used to characterize the suicide attempt at inclusion and those occurring during the follow-up.ResultsPost-DST cortisol level at 9 p.m. was higher in patients with an initial violent or serious suicide attempt than in non-violent/non-serious attempters (p < .010). Higher post-DST cortisol at 9p.m. was associated with lower RRRS rescue score and higher clinical impression of suicide severity at inclusion. Among the 66 patients who completed the follow-up, 26 attempted suicide again at least once. Higher pre-DST cortisol at 8a.m. predicted new suicide attempts during the follow-up (OR = 2.15 [1.11, 4.15]), and higher cortisol Δ index at 9p.m. was associated with higher suicide intent during the follow-up.ConclusionsOur results suggest that HPA axis hyper-reactivity monitored with the DST is a marker of violent/serious suicide attempt with lower rescue possibility. Furthermore, higher changes between pre-DST and post-DST cortisol levels may predict higher suicide intent. These findings might help to characterize the biological features of nearest suicide phenotypes.

Project description:Background: With around 800,000 people taking their own lives every year, suicide is a growing health concern. Understanding the factors that underlie suicidality and identifying specific variables associated with increased risk is paramount for increasing our understanding of suicide etiology. Neuroimaging methods that enable the investigation of structural and functional brain markers in vivo are a promising tool in suicide research. Although a number of studies in clinical samples have been published to date, evidence about neuroimaging correlates for suicidality remains controversial. Objective: Patients with mental disorders have an increased risk for both suicidal behavior and non-suicidal self-injury. This manuscript aims to present an up-to-date overview of the literature on potential neuroimaging markers associated with SB and NSSI in clinical samples. We sought to identify consistently reported structural changes associated with suicidal symptoms within and across psychiatric disorders. Methods: A systematic literature search across four databases was performed to identify all English-language neuroimaging articles involving patients with at least one psychiatric diagnosis and at least one variable assessing SB or NSSI. We evaluated and screened evidence in these articles against a set of inclusion/exclusion criteria and categorized them by disease, adhering to the PRISMA guidelines. Results: Thirty-three original scientific articles investigating neuroimaging correlates of SB in psychiatric samples were found, but no single article focusing on NSSI alone. Associations between suicidality and regions in frontal and temporal cortex were reported by 15 and 9 studies across four disorders, respectively. Furthermore, differences in hippocampus were reported by four studies across three disorders. However, we found a significant lack of replicability (consistency in size and direction) of results across studies. Conclusions: Our systematic review revealed a lack of neuroimaging studies focusing on NSSI in clinical samples. We highlight several potential sources of bias in published studies, and conclude that future studies should implement more rigorous study designs to minimize bias risk. Despite several studies reporting associations between SB and anatomical differences in the frontal cortex, there was a lack of consistency across them. We conclude that better-powered samples, standardized neuroimaging and analytical protocols are needed to continue advancing knowledge in this field.

Project description:BackgroundExposure to suicidal behavior may be associated with increased risk of suicide, suicide attempt, and suicidal ideation and is a significant public health problem. However, evidence to date has not reliably distinguished between exposure to suicide versus suicide attempt, nor whether the risk differs across suicide-related outcomes, which have markedly different public health implications. Our aim therefore was to quantitatively assess the independent risk associated with exposure to suicide and suicide attempt on suicide, suicide attempt, and suicidal ideation outcomes and to identify moderators of this risk using multilevel meta-analysis.Methods and findingsWe systematically searched MEDLINE, Embase, PsycINFO, CINAHL, ASSIA, Sociological Abstracts, IBSS, and Social Services Abstracts from inception to 19 November 2019. Eligible studies included comparative data on prior exposure to suicide, suicide attempt, or suicidal behavior (composite measure-suicide or suicide attempt) and the outcomes of suicide, suicide attempt, and suicidal ideation in relatives, friends, and acquaintances. Dichotomous events or odds ratios (ORs) of suicide, suicide attempt, and suicidal ideation were analyzed using multilevel meta-analyses to accommodate the non-independence of effect sizes. We assessed study quality using the National Heart, Lung, and Blood Institute quality assessment tool for observational studies. Thirty-four independent studies that presented 71 effect sizes (exposure to suicide: k = 42, from 22 independent studies; exposure to suicide attempt: k = 19, from 13 independent studies; exposure to suicidal behavior (composite): k = 10, from 5 independent studies) encompassing 13,923,029 individuals were eligible. Exposure to suicide was associated with increased odds of suicide (11 studies, N = 13,464,582; OR = 3.23, 95% CI = 2.32 to 4.51, P < 0.001) and suicide attempt (10 studies, N = 121,836; OR = 2.91, 95% CI = 2.01 to 4.23, P < 0.001). However, no evidence of an association was observed for suicidal ideation outcomes (2 studies, N = 43,354; OR = 1.85, 95% CI = 0.97 to 3.51, P = 0.06). Exposure to suicide attempt was associated with increased odds of suicide attempt (10 studies, N = 341,793; OR = 3.53, 95% CI = 2.63 to 4.73, P < 0.001), but not suicide death (3 studies, N = 723; OR = 1.64, 95% CI = 0.90 to 2.98, P = 0.11). By contrast, exposure to suicidal behavior (composite) was associated with increased odds of suicide (4 studies, N = 1,479; OR = 3.83, 95% CI = 2.38 to 6.17, P < 0.001) but not suicide attempt (1 study, N = 666; OR = 1.10, 95% CI = 0.69 to 1.76, P = 0.90), a finding that was inconsistent with the separate analyses of exposure to suicide and suicide attempt. Key limitations of this study include fair study quality and the possibility of unmeasured confounders influencing the findings. The review has been prospectively registered with PROSPERO (CRD42018104629).ConclusionsThe findings of this systematic review and meta-analysis indicate that prior exposure to suicide and prior exposure to suicide attempt in the general population are associated with increased odds of subsequent suicidal behavior, but these exposures do not incur uniform risk across the full range of suicide-related outcomes. Therefore, future studies should refrain from combining these exposures into single composite measures of exposure to suicidal behavior. Finally, future studies should consider designing interventions that target suicide-related outcomes in those exposed to suicide and that include efforts to mitigate the adverse effects of exposure to suicide attempt on subsequent suicide attempt outcomes.

Dataset Information

Neuroimaging-informed phenotypes of suicidal behavior: a family history of suicide and the use of a violent suicidal means.

Publications

Neuroimaging-informed phenotypes of suicidal behavior: a family history of suicide and the use of a violent suicidal means.

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