Transcutaneous Auricular Vagus Nerve Stimulation in Adolescent Treatment Resistant Depression-A Case Report.

Adolescence is a critical time period for the onset of depression, and many patients do not respond to treatment. Transcutaneous auricular vagus nerve stimulation may be a promising alternative. Here, we present the case of an adolescent girl with treatment-resistant depression who received transcutaneous auricular vagus nerve stimulation over the course of 7.5 months.

A paucity of evidence in youth: The curious case of transcranial direct current stimulation for depression.

A significant proportion of youth with depression do not respond to available treatment. Transcranial direct current stimulation (tDCS) is a promising third-line treatment in depressed adults, but evidence in youth seems scarce. Following the PRISMA guidelines, we conducted a systematic literature review on tDCS treatment for depression in children and adolescents. No published studies were found on the use of tDCS in youth with depression. Given the null-findings, no conclusion can be drawn about the effectiveness of tDCS treatment for adolescent depression. The reasons for this paucity of evidence in light of existing regulatory frameworks and technical challenges are discussed.

Pharmacological anti-inflammatory treatment in children and adolescents with depressive symptoms: A systematic-review and meta-analysis.

Growing evidence suggests an association between inflammatory processes and depressive disorders (DD). DD typically emerge during adolescence. Treatment effects of agents with anti-inflammatory properties in youth DD have not been systematically reviewed. Here, the existing evidence on the use of anti-inflammatory drugs (including polyunsaturated fatty acids, nonsteroidal anti-inflammatory drugs, cytokine inhibitors, statins, pioglitazone, corticosteroids, and minocycline or modafinil) in children and adolescents with DD was synthesized using meta-analysis. The PROSPERO preregistered search yielded 22 records meeting search criteria. Of these, data from 19 primary studies (n = 1366 subjects) were subjected to meta-analysis. A significant but small effect in favor of anti-inflammatory agents in reducing depressive symptoms in youth with DD was found (SMD = -0.29, 95 % CI = -0.514; -0.063, p = 0.01). Post-hoc analyzes of drug subclasses found a significant effect of omega-3 fatty acids in reducing depressive symptoms. Results underline the importance to consider inflammatory pathways in the supplemental treatment of youth with DD. Further research is warranted, to clarify if anti-inflammatory agents are only effective in a subpopulation of patients (inflammatory biotype of depression in youth) and/or to alleviate specific symptom domains of depression (e.g., cognitive symptoms).

Movement initiation and preparation in subjects with schizophrenia - The amplitude of the readiness potential as a biological marker for negative symptom severity.

OBJECTIVE: Despite extensive research, the etiology of negative symptoms is not well understood. Preliminary findings are linking motor disturbances to negative symptom severity. We aimed to further the understanding to what extent motor movement preparation influences negative symptom severity. METHODS: In a cohort of 31 subjects with schizophrenia and 20 control subjects we recorded the readiness potential amplitude over Cz during spontaneous movements of the right and left thumb. We further assessed negative and positive symptom severity (scale for the assessment of negative and positive symptoms) as well as neurological soft signs (NSS). RESULTS: In subjects with schizophrenia the severity of negative symptoms was best predicted by the readiness potential amplitude and the NSS subdomain motor coordination. The correlation between deficits in motor coordination and negative symptom severity was partially mediated by the readiness potential amplitude in subjects with schizophrenia. CONCLUSIONS: Deficits in motor processing are linked to negative symptom severity in schizophrenia. The readiness potential may represent a biological marker of these basal deficits. In combination with the assessment of NSS, the readiness potential may be a marker of the course of negative symptom severity and help clarifying interdependencies between (pre)frontal networks for action initiation and coordination, as well as negative symptoms.

Red cell distribution width and depressive symptoms: A failed replication in female adolescents.

OBJECTIVES: Despite the increasingly high prevalence and serious consequences of depression in adolescents, there is a lack of economical and reliable biomarkers to aid the diagnostic process. Recent findings suggest that red blood cell distribution width (RDW) is an easily obtainable biomarker of depression in adults. Here, we aimed to replicate the finding of increased RDW in clinically depressed adolescents. METHODS: Data from depressed adolescent female patients (n = 93) and healthy controls (HC) (n = 43) aged 12-17 years from the AtR!Sk-bio cohort study were retrospectively analysed. We compared RDW between groups and tested whether there was an association between RDW and depression severity and global (psychiatric) symptom severity. We also examined the influence of age on RDW. RESULTS: There was no significant difference between depressed patients and healthy controls and no association between RDW and depression severity. However, higher RDW values were associated with greater global symptom severity. Regardless of group, there was a positive association between RDW and age. CONCLUSIONS: RDW appears to be unfit as an aid for clinical diagnosis of depression in adolescents, but may be useful in assessing global psychiatric symptom burden.

Predictors of treatment non-response for depression in a sample of female adolescents with risk-taking and self-injurious behavior - A one year follow-up.

OBJECTIVE: Depressive disorders (DD) are highly prevalent among adolescents. While up to 60 % do not respond to treatment, evidence on predictors of treatment non-response in this age group is mixed, impeding meaningful clinical implications. Drawing on a consecutive clinical cohort of adolescents with risk taking and self-injurious behavior, the present study aimed to identify predictors of treatment non-response for female DD in a naturalistic one year follow-up. METHODS: The sample comprised female adolescents with verified DD (n = 152). Patients underwent assessments at baseline (T0) and follow-up (T1). Sociodemographic factors (e.g., age), clinical measures (e.g., symptom severity, trauma), and treatment variables (e.g. number of psychotherapy sessions), were analyzed as potential predictors of treatment non-response in unadjusted analyses and analyses adjusting for treatment intensity and age at baseline. Treatment response was defined based on not fulfilling formal diagnosis for DD at follow-up (52.3 %; n = 80) or the 50 % decrease in self-reported depressive symptoms (21.1 %; n = 32) from T0 to T1. RESULTS: Greater depressive and overall symptom severity, greater frequency of self-injuries, history of suicide attempts and history of childhood trauma at T0 were robustly associated with treatment non-response based on diagnostic interviews. Only a lower number of siblings was robustly associated with treatment non-response based on self-reports. LIMITATIONS: Findings may not generalize to other treatment settings. CONCLUSION: Collectively, our results highlight overall symptom severity as significant predictor of treatment non-response in female adolescents with depression. Methodological differences (interviews versus self-reports) and potential implications from these findings for clinical practice are discussed.

Transcranial magnetic stimulation in the treatment of adolescent depression: a systematic review and meta-analysis of aggregated and individual-patient data from uncontrolled studies.

Transcranial magnetic stimulation (TMS) is a non-invasive treatment for adolescent major depressive disorder (MDD). Existing evidence on the efficacy of TMS in adolescent MDD awaits quantitative synthesis. A systematic literature search was conducted, and data from eligible studies were synthesized using random-effects models. Treatment-covariate interactions were examined in exploratory analyses of individual-patient data (IPD). Systematic search of the literature yielded 1264 hits, of which 10 individual studies (2 randomized trials) were included for quantitative synthesis of mainly uncontrolled studies. Individual patient data (IPD) were available from five trials (all uncontrolled studies). Quantitative synthesis of aggregated data revealed a statistically significant negative overall standardized mean change (pooled SMCC = 2.04, 95% CI [1.46; 2.61], SE = 0.29, p < .001), as well as a significant overall treatment response rate (Transformed Proportion = 41.30%, 95% CI [31.03; 51.57], SE = 0.05; p < 0.001), considering data from baseline to post-treatment. Exploratory IPD analyses suggests TMS might be more effective in younger individuals and individuals with more severe depression, and efficacy might be enhanced with certain treatment modality settings, including higher number of TMS sessions, longer treatment durations, and unilateral and not bilateral stimulation. Existing studies exhibit methodological shortcomings, including small-study effects and lack of control group, blinding, and randomization-compromising the credibility of the present results. To date, two randomized controlled trials on TMS in adolescent depression have been published, and the only large-scale randomized trial suggests TMS is not more effective than sham stimulation. Future large-scale, randomized, and sham-controlled trials are warranted. Future trials should ensure appropriate selection of patients for TMS treatment and guide precision medicine approaches for stimulation protocols.