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Cortical inhibitory markers of lifetime suicidal behavior in depressed adolescents.

ABSTRACT: Although suicide is the second-leading cause of death in adolescents and young adults worldwide, little progress has been made in developing reliable biological markers of suicide risk and suicidal behavior. Converging evidence suggests that excitatory and inhibitory cortical processes mediated by the neurotransmitters glutamate and ?-aminobutyric acid (GABA) are dysregulated in suicidal individuals. This study utilized single- and paired-pulse transcranial magnetic stimulation (TMS) to assess excitatory and inhibitory cortical functioning in healthy control adolescents (n?=?20), depressed adolescents without any history of suicidal behavior ("Depressed", n?=?37), and depressed adolescents with lifetime history of suicidal behavior ("Depressed+SB", n?=?17). In a fixed-effects general linear model analysis, with age, sex, and depression severity as covariates, no significant group main effects emerged for resting motor threshold, intracortical facilitation, short-interval intracortical inhibition, or cortical silent period. However, group main effects were significant for long-interval intracortical inhibition (LICI) at interstimulus intervals (ISIs) of 100?ms and 150?ms, but not 200?ms. Depressed+SB adolescents demonstrated impaired LICI compared to healthy control and Depressed adolescents, while healthy control and Depressed participants did not differ in LICI. Multiple linear robust regression revealed significant positive linear relationships between lifetime suicidal behavior severity and impairment in LICI at 100-ms and 150-ms ISIs. In a post hoc receiver operating characteristic analysis, LICI significantly discriminated Depressed from Depressed+SB youth in 100-ms and 150-ms paradigms. These findings suggest that GABA_B receptor-mediated inhibition is distinctly dysregulated in depressed adolescents with histories of suicidal behavior. Further research is warranted to establish the utility of cortical inhibition in the assessment of suicide risk and as a target for treatment interventions.

SUBMITTER: Lewis CP

PROVIDER: S-EPMC6046050 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Cortical inhibitory markers of lifetime suicidal behavior in depressed adolescents.

Lewis Charles P CP Nakonezny Paul A PA Blacker Caren J CJ Vande Voort Jennifer L JL Port John D JD Worrell Gregory A GA Jo Hang Joon HJ Daskalakis Zafiris J ZJ Croarkin Paul E PE

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20180314 9

Although suicide is the second-leading cause of death in adolescents and young adults worldwide, little progress has been made in developing reliable biological markers of suicide risk and suicidal behavior. Converging evidence suggests that excitatory and inhibitory cortical processes mediated by the neurotransmitters glutamate and γ-aminobutyric acid (GABA) are dysregulated in suicidal individuals. This study utilized single- and paired-pulse transcranial magnetic stimulation (TMS) to assess e ...[more]

PMID: 29703993

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Project description:ContextSuicide is the second leading cause of death in adolescents and young adults in Europe. Reducing suicides is therefore a key public health target. Previous studies have shown associations between suicidal behaviors, depression and family factors.ObjectiveTo assess the role of family factors in depression and suicidality in a large community-based sample of adolescents and to explore specific contributions (e.g. mother vs. father; conflict vs. no conflict; separation vs. no separation) taking into account other risk factors.MethodsA cross-sectional sample of adolescents aged 17 years was recruited in 2008. 36,757 French adolescents (18,593 girls and 18,164 boys) completed a questionnaire including socio-demographic characteristics, drug use, family variables, suicidal ideations and attempts. Current depression was assessed with the Adolescent Depression Rating Scale (ADRS). Adolescents were divided into 4 groups according to suicide risk severity (grade 1 = depressed without suicidal ideation and without suicide attempts, grade 2 = depressed with suicidal ideations and grade 3 = depressed with suicide attempts; grade 0 = control group). Multivariate regressions were applied to assess the Odds Ratio of potential risk factors comparing grade 1, 2 or 3 risk with grade 0.Results7.5% of adolescents (10.4% among girls vs. 4.5% among boys) had ADRS scores compatible with depression; 16.2% reported suicidal ideations in the past 12 months and 8.2% reported lifetime suicide attempts. Repeating a year in school was significantly associated to severity grade of suicide risk (1 and 3), as well as all substance use, tobacco use (severity grades 2 and 3) and marijuana use (severity grade 3), for girls and boys. After adjustment, negative relationships with either or both parents, and parents living together but with a negative relationship were significantly associated with suicide risk and/or depression in both genders (all risk grades), and Odds Ratios increased according to risk severity grade.ConclusionFamily discord and negative relationship with parents were associated with an increased suicide risk in depressed adolescents. So it appears essential to take intrafamilial relationships into account in depressed adolescents to prevent suicidal behaviours.

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Cortical inhibitory markers of lifetime suicidal behavior in depressed adolescents.

Publications

Cortical inhibitory markers of lifetime suicidal behavior in depressed adolescents.

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