Event-Related Potential Markers of Suicidality in Adolescents.

BACKGROUND: Implicit cognitive markers may assist with the prediction of suicidality beyond clinical risk factors. The aim of this study was to investigate neural correlates associated with the Death/Suicide Implicit Association Test (DS-IAT) via event-related potentials (ERP) in suicidal adolescents. METHODS: Thirty inpatient adolescents with suicidal ideations and behaviors (SIBS) and 30 healthy controls from the community were recruited. All participants underwent 64-channel electroencephalography, DS-IAT, and clinical assessments. Hierarchical generalized linear models with spatiotemporal clustering were used to identify significant ERPs associated with the behavioral outcome of DS-IAT (D scores) and group differences. RESULTS: Behavioral results (D scores) showed that the adolescents with SIBS had stronger implicit associations between "death" and "self" than the healthy group (P = .02). Within adolescents with SIBS, participants with stronger implicit associations between "death" and "self" reported more difficulty in controllability of suicidal ideation in the past 2 weeks based on the Columbia-Suicide Severity Rating Scale (P = .03). For the ERP data, the D scores and N100 component over the left parieto-occipital cortex had significant correlations. Significant group differences without behavioral correlation were observed for a second N100 cluster (P = .01), P200 (P = .02), and late positive potential (5 clusters, all P ≤ .02). Exploratory predictive models combining both neurophysiological and clinical measures distinguished adolescents with SIBS from healthy adolescents. CONCLUSIONS: Our results suggest that N100 may be a marker of attentional resources involved in the distinction of stimuli that are congruent or incongruent to associations between death and self. Combined clinical and ERP measures may have utility in future refinements of assessment and treatment approaches for adolescents with suicidality.

Transcranial Magnetic Stimulation Markers of Antidepressant Treatment in Adolescents With Major Depressive Disorder.

BACKGROUND: The goal of this study was to examine baseline transcranial magnetic stimulation measures of cortical inhibition and excitability in depressed patients and characterize their longitudinal posttreatment changes. METHODS: Fifteen adolescents (age 13-17 years) with moderate to severe major depressive disorder and 22 healthy controls (age 9-17) underwent single- and paired-pulse transcranial magnetic stimulation and clinical assessments. Transcranial magnetic stimulation measures included short-interval intracortical inhibition (2 and 4 milliseconds), long-interval intracortical inhibition (100, 150, and 200 milliseconds), cortical silent period, and intracortical facilitation (10, 15, and 20 milliseconds). Ten participants with major depressive disorder initiated antidepressant treatment or had dose adjustments. These participants were reassessed after treatment. Depression symptom severity was measured with the Children's Depression Rating Scale, Revised. Robust regression modeling compared healthy and depressed adolescents at baseline. Relationships between changes in cortical inhibition and changes in depressive symptom severity were assessed in the depressed adolescents receiving antidepressant treatment. RESULTS: Our results revealed that at baseline, short-interval intracortical inhibition-2 was significantly reduced (Padj = .01) in depressed participants, suggesting impaired cortical inhibition compared with healthy controls. At follow-up, improvement in Children's Depression Rating Scale, Revised scores correlated with improvement in short-interval intracortical inhibition-4 amplitude (greater inhibition) after antidepressant treatment (R2 = 0.63; P = .01). CONCLUSIONS: These results suggest that cortical inhibition measures may have promise as biomarkers in adolescents treated for depression.

Trajectory Modeling and Response Prediction in Transcranial Magnetic Stimulation for Depression.

Repetitive transcranial magnetic stimulation (rTMS) therapy could be improved by better and earlier prediction of response. Latent class mixture (LCMM) and non-linear mixed effects (NLME) modelling have been applied to model the trajectories of antidepressant response (or non-response) to TMS, but it is not known whether such models can predict clinical outcomes. We compared LCMM and NLME approaches to model the antidepressant response to TMS in a naturalistic sample of 238 patients receiving rTMS for treatment resistant depression (TRD), across multiple coils and protocols. We then compared the predictive power of those models. LCMM trajectories were influenced largely by baseline symptom severity, but baseline symptoms provided little predictive power for later antidepressant response. Rather, the optimal LCMM model was a nonlinear two-class model that accounted for baseline symptoms. This model accurately predicted patient response at 4 weeks of treatment (AUC = 0.70, 95% CI = [0.52-0.87]), but not before. NLME offered slightly improved predictive performance at 4 weeks of treatment (AUC = 0.76, 95% CI = [0.58 - 0.94], but likewise, not before. In showing the predictive validity of these approaches to model response trajectories to rTMS, we provided preliminary evidence that trajectory modeling could be used to guide future treatment decisions.

Preliminary Evidence for Anhedonia as a Marker of Sexual Trauma in Female Adolescents.

INTRODUCTION: Major depressive disorder (MDD) is a common condition with heterogeneous presentations that often include predominant anhedonia. Previous studies have revealed that childhood trauma is a potent risk factor for the development of MDD; however, the clinical implications of this finding are not fully understood. METHODS: Participants were adolescents (age 13-21 years) with a diagnosis of moderate-to-severe major depressive disorder and healthy controls. We used generalized linear models to assess the relationship between anhedonia severity and trauma severity in a cross-sectional dataset. RESULTS: This cross-sectional analysis of an adolescent sample that underwent clinical evaluations and a trauma assessment, suggested that anhedonia was associated with historical trauma severity. The association between anhedonia and sexual abuse was greater in female participants compared to male participants. DISCUSSION: Our results were partially in line with the reported literature in adult samples. Future studies aiming to characterize the trauma-anhedonia relationship in adolescents should utilize scales designed specifically to measure these constructs in young populations, and scales that assess specific subtypes of anhedonia.

A Systematic Review of Neuromodulation Treatment Effects on Suicidality.

Introduction: Neuromodulation is an important group of therapeutic modalities for neuropsychiatric disorders. Prior studies have focused on efficacy and adverse events associated with neuromodulation. Less is known regarding the influence of neuromodulation treatments on suicidality. This systematic review sought to examine the effects of various neuromodulation techniques on suicidality. Methods: A systematic review of the literature from 1940 to 2020 following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline was conducted. Any reported suicide-related outcome, including suicidal ideation, suicide intent, suicide attempt, completed suicide in reports were considered as a putative measure of treatment effect on suicidality. Results: The review identified 129 relevant studies. An exploratory analysis of a randomized controlled trial comparing the effects of sertraline and transcranial direct-current stimulation (tDCS) for treating depression reported a decrease in suicidal ideation favoring tDCS vs. placebo and tDCS combined with sertraline vs. placebo. Several studies reported an association between repetitive transcranial magnetic stimulation and improvements in suicidal ideation. In 12 of the studies, suicidality was the primary outcome, ten of which showed a significant improvement in suicidal ideation. Electroconvulsive therapy (ECT) and magnetic seizure therapy was also shown to be associated with lower suicidal ideation and completed suicide rates. There were 11 studies which suicidality was the primary outcome and seven of these showed an improvement in suicidal ideation or suicide intent and fewer suicide attempts or completed suicides in patients treated with ECT. There was limited literature focused on the potential protective effect of vagal nerve stimulation with respect to suicidal ideation. Data were mixed regarding the potential effects of deep brain stimulation on suicidality. Conclusions: Future prospective studies of neuromodulation that focus on the primary outcome of suicidality are urgently needed. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=125599, identifier: CRD42019125599.

Psychometric Properties of the Patient Health Questionnaire-9 Modified for Major Depressive Disorder in Adolescents.

OBJECTIVES: The Patient Health Questionnaire-9 Modified (PHQ-9M) is a self-report tool used to assess the presence and severity of depressive symptoms in teenagers. Despite widespread use in primary care clinics and psychiatric settings, the PHQ-9M has not been validated nor are its psychometric properties adequately understood for the adolescent population. This study sought to examine the psychometrics of the PHQ-9M in treatment-seeking, depressed adolescents at a psychiatric psychopharmacology clinic who were concurrently assessed with the Children's Depression Rating Scale Revised (CDRS-R) and Quick Inventory of Depressive Symptomatology-Adolescent (17-item) Self-Report (QIDS-A17-SR). METHODS: Adolescents (N = 160) aged 13 through 18 years with a diagnosis of major depressive disorder, determined on the basis of a clinical interview and semi-structured interview using the Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version, were assessed for severity of depressive symptoms with the PHQ-9M, CDRS-R (adolescent interview only), and QIDS-A17-SR assessments at baseline, 4, and 8 weeks. Classical test theory analysis was used to evaluate the internal consistency and dimensionality of the PHQ-9M. Convergent validity was evaluated via intraclass correlations of the PHQ-9M with the CDRS-R and QIDS-A17-SR. Sensitivity to treatment response was also evaluated. RESULTS: The internal consistency (Cronbach's coefficient α) at baseline, 4, and 8 weeks was 0.879, 0.859, and 0.827 for the PHQ-9M; 0.739, 0.835, and 0.867 for CDRS-R; and 0.712, 0.777, and 0.804 for QIDS-A17-SR, respectively. The PHQ-9M had moderate convergent validity with the CDRS-R but good convergent validity with the QIDS-A17-SR. The PHQ-9M was less sensitive to changes in symptom severity than the CDRS-R and QIDS-A17-SR. CONCLUSIONS: The PHQ-9M appears to be a valid and reliable assessment tool for the severity of depressive symptoms in a psychiatric clinic setting. However, its utility as a treatment outcome measure may be limited compared with other available rating scales.