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Alterations in functional brain networks in depressed patients with a suicide attempt history.

ABSTRACT: Suicide is a major challenge in public health and is strongly associated with major depressive disorder (MDD). Despite recent neuroimaging developments, the neural correlates of suicide behavior in patients with MDD remain unclear. Independent component analysis (ICA) for neuroimaging data allows the identification of functional brain networks without prior regions of interest and may help to identify neurobiological markers of specific disorders. Using ICA, we investigated the differences in resting-state brain networks in patients with MDD who had or did not have a history of suicide attempts and in healthy controls (HCs). Suicidal depressed (SD) patients, non-suicidal depressed (NSD) patients, and HCs significantly differed from each other in the pattern of connectivity of multiple functional networks, network synchronization, and functional network connectivity (FNC). The patient groups had a decreased network synchronization in the insular, cerebellum, basal ganglia, thalamus, operculum, frontoparietal cortices, and sensory cortices relative to the HCs. The decreased FNC between these networks (insular-default mode network and insular-cerebellum) was found in the SD group compared to the NSD and HC groups. These differences were not related to illness duration and medication status differences between SD and NSD. Furthermore, the degree of FNC in these networks was associated with the suicide ideation and stress level. Our results demonstrated that widespread but discrete network changes in brain networks and their interconnectivity was associated with suicide attempts in patients with MDD. Our results suggest that the neural basis underlying the psychopathology of attempted suicide in patients with MDD involves multiple brain networks and their interaction.

SUBMITTER: Jung J

PROVIDER: S-EPMC7162936 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Understanding the neural mechanisms of suicidal behavior is crucial. While regional brain alterations have previously been reported, knowledge about brain functional connectomics is currently limited. Here, we investigated differences in global topologic network properties and local network-based functional organization in both suicide attempters and suicide relatives. Two independent samples of depressed suicide attempters (N?=?42), depressed patient controls (N?=?43), healthy controls (N?=?66) as well as one sample of healthy relatives of suicide victims (N?=?16) and relatives of depressed patients (N?=?16) were investigated with functional magnetic resonance imaging in the resting-state condition. Graph theory analyses were performed. Assortativity, clustering coefficients, global efficiency, and rich-club coefficients were calculated. A network-based statistic approach was finally used to examine functional connectivity matrices. In comparison to healthy controls, both patient groups showed significant reduction in assortativity, and decreased functional connectivity in largely central and posterior brain networks. Suicide attempters only differed from patient controls in terms of higher rich-club coefficients for the highest degree nodes. Compared to patient relatives and healthy controls, suicide relatives showed reduced assortativity, reduced clustering coefficients, increased global efficiency, and increased rich-club coefficients for the highest degree nodes. Suicide relatives also showed reduced functional connectivity in one anterior and one posterior sub-network in comparison to healthy controls, and in a largely anterior brain network in comparison to patient relatives. In conclusion, these results suggest that the vulnerability to suicidal behavior may be associated with heritable deficits in global brain functioning - characterized by weak resilience and poor segregation - and in functional organization with reduced connectivities affecting the ventral and dorsal prefrontal cortex, the anterior cingulate, thalamus, striatum, and possibly the insula, fusiform gyrus and the cerebellum.

Project description:ImportanceMental health of soldiers is adversely affected by the death and injury of other unit members, but whether risk of suicide attempt is influenced by previous suicide attempts in a soldier's unit is unknown.ObjectiveTo examine whether a soldier's risk of suicide attempt is influenced by previous suicide attempts in that soldier's unit.Design, setting, and participantsUsing administrative data from the Army Study to Assess Risk and Resilience in Servicemembers (STARRS), this study identified person-month records for all active-duty, regular US Army, enlisted soldiers who attempted suicide from January 1, 2004, through December 31, 2009 (n = 9650), and an equal-probability sample of control person-months (n = 153 528). Data analysis was performed from August 8, 2016, to April 10, 2017.Main outcomes and measuresLogistic regression analyses examined the number of past-year suicide attempts in a soldier's unit as a predictor of subsequent suicide attempt, controlling for sociodemographic features, service-related characteristics, prior mental health diagnosis, and other unit variables, including suicide-, combat-, and unintentional injury-related unit deaths. The study also examined whether the influence of previous unit suicide attempts varied by military occupational specialty (MOS) and unit size.ResultsOf the final analytic sample of 9512 enlisted soldiers who attempted suicide and 151 526 control person-months, most were male (86.4%), 29 years or younger (68.4%), younger than 21 years when entering the army (62.2%), white (59.8%), high school educated (76.6%), and currently married (54.8%). In adjusted models, soldiers were more likely to attempt suicide if 1 or more suicide attempts occurred in their unit during the past year (odds ratios [ORs], 1.4-2.3; P < .001), with odds increasing as the number of unit attempts increased. The odds of suicide attempt among soldiers in a unit with 5 or more past-year attempts was more than twice that of soldiers in a unit with no previous attempts (OR, 2.3; 95% CI, 2.1-2.6). The association of previous unit suicide attempts with subsequent risk was significant whether soldiers had a combat arms MOS or other MOS (ORs, 1.4-2.3; P < .001) and regardless of unit size, with the highest risk among those in smaller units (1-40 soldiers) (ORs, 2.1-5.9; P < .001). The population-attributable risk proportion for 1 or more unit suicide attempts in the past year indicated that, if this risk could be reduced to no unit attempts, 18.2% of attempts would not occur.Conclusions and relevanceRisk of suicide attempt among soldiers increased as the number of past-year suicide attempts within their unit increased for combat arms and other MOSs and for units of any size but particularly for smaller units. Units with a history of suicide attempts may be important targets for preventive interventions.

Project description:A consistent body of evidence supports a role of reduced neurotrophic signaling in the pathophysiology of major depressive disorder (MDD) and suicidal behavior. Especially in suicide victims, lower postmortem brain messenger RNA and protein levels of neurotrophins and their receptors have been reported.To determine whether the brain-derived neurotrophic factor (BDNF) gene or its high-affinity receptor gene, receptor tyrosine kinase 2 (NTRK2), confer risk for suicide attempt (SA) and MDD by investigating common genetic variants in these loci.Eighty-three tagging single-nucleotide polymorphisms (SNPs) covering the genetic variability of these loci in European populations were assessed in a case-control association design.Inpatients and screened control subjects.The discovery sample consisted of 394 depressed patients, of whom 113 had SA, and 366 matched healthy control subjects. The replication studies comprised 744 German patients with MDD and 921 African American nonpsychiatric clinic patients, of whom 152 and 119 were positive for SA, respectively.Blood or saliva samples were collected from each participant for DNA extraction and genotyping.Associations of SNPs in BDNF and NTRK2 with SA and MDD.Independent SNPs within NTRK2 were associated with SA among depressed patients of the discovery sample that could be confirmed in both the German and African American replication samples. Multilocus interaction analysis revealed that single SNP associations within this locus contribute to the risk of SA in a multiplicative and interactive fashion (P = 4.7 x 10(-7) for a 3-SNP model in the combined German sample). The effect size was 4.5 (95% confidence interval, 2.1-9.8) when patients carrying risk genotypes in all 3 markers were compared with those without any of the 3 risk genotypes.Our results suggest that a combination of several independent risk alleles within the NTRK2 locus is associated with SA in depressed patients, further supporting a role of neurotrophins in the pathophysiology of suicide.

Project description:Social exclusion is associated with greater suicide risk and more needs to be known about the biological processes contributing to this association. Oxytocin, a neuropeptide that regulates social interactions, may protect against the negative effects of exclusion by motivating social engagement. Oxytocin levels and desire for social engagement increase when non-psychiatric controls experience acute social exclusion. However, among individuals with borderline personality disorder and chronic depression, oxytocin levels decrease following exclusion. Both of these psychiatric illnesses are associated with high rates of suicidal behavior. No research has examined changes in oxytocin following social exclusion among individuals at risk for suicide. This quasi-experimental study examined differences in oxytocin levels and perceptions of social connectedness following an in-laboratory, acute social exclusion task among (a) individuals with no depression or suicide attempt histories, (b) individuals with current depression symptoms, and (c) individuals with current depression symptoms and suicide attempt histories. Young adults (N = 100) completed self-report measures and provided blood samples before and after an acute social exclusion task (Cyberball). Oxytocin was quantified via enzyme-linked immunosorbent assay. Mixed-design ANCOVAs were used to evaluate changes in unextracted and extracted oxytocin levels, desire for emotional support, thwarted belongingness, and perceived burdensomeness. Among suicide attempters, unextracted oxytocin levels decreased and desire for emotional support did not significantly change following exclusion. Among depressed and healthy controls, desire for emotional support increased and unextracted oxytocin levels did not significantly change. No significant changes in extracted oxytocin levels, thwarted belongingness and perceived burdensomeness emerged. Further research is needed to determine if dysregulated oxytocin-related processes biologically predispose individuals with suicide attempt histories to greater social disconnection and suicide risk.

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Alterations in functional brain networks in depressed patients with a suicide attempt history.

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