Suicide is the second leading cause of death in 12- to 17-year-old adolescents in the USA. Research on biological mechanisms contributing to self-harm risk that could be targeted in treatment could help to prevent suicide and self-harm episodes.

We aimed to evaluate whether markers of inflammation, interleukin-6 (IL-6) and C-reactive protein (CRP), predict self-harm over 3 months within a sample selected for elevated suicide/self-harm risk at project entry.

Fifty-one adolescents aged 12–19 years selected for elevated suicide/self-harm risk completed three clinical interviews about suicide attempts and non-suicidal self-injury, 3 months apart. At baseline and 3 months, youth also provided blood samples, from which we assayed levels of IL-6 and CRP.

Using generalised mixed models, we found that greater levels of IL-6 predicted more self-harm episodes (odds ratio [OR] = 3.3, 95% CI: 1.1, 10.0) and specifically, non-suicidal self-injury (OR = 3.5, 95% CI: 1.1, 11.2), over 3 months.

The study findings increase our understanding of whether and how inflammation may be implicated in risk of self-harm. IL-6 may be a viable biological marker of short-term risk for self-harm.

Electroconvulsive therapy (ECT) is effective for treatment-resistant depression and leads to short-term structural brain changes and decreases in the inflammatory response. However, little is known about how brain structure and inflammation relate to the heterogeneity of treatment response in the months following an index ECT course.

A naturalistic six-month study following an index ECT course included 20 subjects with treatment-resistant depression. Upon conclusion of the index ECT course and again after six months, structural magnetic resonance imaging scans and peripheral inflammation measures [interleukin-6 (IL-6), IL-8, tumor necrosis factor (TNF-α), and C-reactive protein] were obtained. Voxel-based morphometry processed with the CAT-12 Toolbox was used to estimate changes in gray matter volume.

Between the end of the index ECT course and the end of follow-up, we found four clusters of significant decreases in gray matter volume (p < 0.01, FWE) and no regions of increased volume. Decreased HAM-D scores were significantly related only to reduced IL-8 level. Decreased volume in one cluster, which included the right insula and Brodmann's Area 22, was related to increased HAM-D scores over six months. IL-8 levels did not mediate or moderate the relationship between volumetric change and depression.

Six months after an index ECT course, multiple regions of decreased gray matter volume were observed in a naturalistic setting. The independent relations between brain volume and inflammation to depressive symptoms suggest novel explanations of the heterogeneity of longer-term ECT treatment response.

Depressive symptoms, such as depressed mood, are common in older adults and associated with an increased risk for morbidity and mortality. Given the evidence that sleep disturbance and alterations in interferon (IFN)-γ biology are associated with depression risk, this study examines the separate and joint contributions of poor sleep maintenance and IFN-γ to depressed mood in older adults.

Community-dwelling, non-depressed older adults (n = 36, 72.1 ± 6.8 years) underwent a night of polysomnography to assess sleep maintenance [i.e. wake time after sleep onset (WASO)]. The morning after polysomnography, plasma levels of IFN-γ were evaluated along with self-reported depressed mood throughout the day. Multivariate linear regression tested associations of WASO and IFN-γ with the severity of depressed mood. In addition, moderation and mediation models examined the role of IFN-γ for the relationship between WASO and depressed mood.

A greater amount of WASO (p < 0.05) and higher levels of IFN-γ (p < 0.01) were both associated with the severity of depressed mood. Moreover, IFN-γ moderated the relationship between WASO and depressed mood (p < 0.01), such that WASO was more strongly related to the depressed mood among those with higher IFN-γ, than among those with lower IFN-γ. However, IFN-γ did not mediate the relationship between WASO and depressed mood.

In this study of older adults, poor sleep maintenance and higher levels of IFN-γ were both related to depressed mood. Moreover, IFN-γ moderated the relationship between poor sleep maintenance and depressed mood. Together, these findings suggest that older adults with higher IFN-γ are at heightened risk for depressive symptoms following sleep disturbance.

Although potential links between oxytocin (OT), vasopressin (AVP), and social cognition are well-grounded theoretically, most studies have included all male samples, and few have demonstrated consistent effects of either neuropeptide on mentalizing (i.e. understanding the mental states of others). To understand the potential of either neuropeptide as a pharmacological treatment for individuals with impairments in social cognition, it is important to demonstrate the beneficial effects of OT and AVP on mentalizing in healthy individuals.

In the present randomized, double-blind, placebo-controlled study (n = 186) of healthy individuals, we examined the effects of OT and AVP administration on behavioral responses and neural activity in response to a mentalizing task.

Relative to placebo, neither drug showed an effect on task reaction time or accuracy, nor on whole-brain neural activation or functional connectivity observed within brain networks associated with mentalizing. Exploratory analyses included several variables previously shown to moderate OT's effects on social processes (e.g., self-reported empathy, alexithymia) but resulted in no significant interaction effects.

Results add to a growing literature demonstrating that intranasal administration of OT and AVP may have a more limited effect on social cognition, at both the behavioral and neural level, than initially assumed. Randomized controlled trial registrations: ClinicalTrials.gov; NCT02393443; NCT02393456; NCT02394054.

Childhood trauma (CT) increases the risk of adult depression. Buffering effects require an understanding of the underlying persistent risk pathways. This study examined whether daily psychological stress processes – how an individual interprets and affectively responds to minor everyday events – mediate the effect of CT on adult depressive symptoms.

Middle-aged women (N = 183) reported CT at baseline and completed daily diaries of threat appraisals and negative evening affect for 7 days at baseline, 9, and 18 months. Depressive symptoms were measured across the 1.5-year period. Mediation was examined using multilevel structural equation modeling.

Reported CT predicted greater depressive symptoms over the 1.5-year time period (estimate = 0.27, s.e. = 0.07, 95% CI 0.15–0.38, p < 0.001). Daily threat appraisals and negative affect mediated the effect of reported CT on depressive symptoms (estimate = 0.34, s.e. = 0.08, 95% CI 0.22–0.46, p < 0.001). Daily threat appraisals explained more than half of this effect (estimate = 0.19, s.e. = 0.07, 95% CI 0.08–0.30, p = 0.004). Post hoc analyses in individuals who reported at least moderate severity of CT showed that lower threat appraisals buffered depressive symptoms. A similar pattern was found in individuals who reported no/low severity of CT.

A reported history of CT acts as a latent vulnerability, exaggerating threat appraisals of everyday events, which trigger greater negative evening affect – processes that have important mental health consequences and may provide malleable intervention targets.

An inflammation-induced imbalance in the kynurenine pathway (KP) has been reported in major depressive disorder but the utility of these metabolites as predictive or therapeutic biomarkers of behavioral activation (BA) therapy is unknown.

Serum samples were provided by 56 depressed individuals before BA therapy and 29 of these individuals also provided samples after 10 weeks of therapy to measure cytokines and KP metabolites. The PROMIS Depression Scale (PROMIS-D) and the Sheehan Disability Scale were administered weekly and the Beck depression inventory was administered pre- and post-therapy. Data were analyzed with linear mixed-effect, general linear, and logistic regression models. The primary outcome for the biomarker analyses was the ratio of kynurenic acid to quinolinic acid (KynA/QA).

BA decreased depression and disability scores (p's < 0.001, Cohen's d's > 0.5). KynA/QA significantly increased at post-therapy relative to baseline (p < 0.001, d = 2.2), an effect driven by a decrease in QA post-therapy (p < 0.001, uncorrected, d = 3.39). A trend towards a decrease in the ratio of kynurenine to tryptophan (KYN/TRP) was also observed (p = 0.054, uncorrected, d = 0.78). Neither the change in KynA/QA, nor baseline KynA/QA were associated with response to BA therapy.

The current findings together with previous research show that electronconvulsive therapy, escitalopram, and ketamine decrease concentrations of the neurotoxin, QA, raise the possibility that a common therapeutic mechanism underlies diverse forms of anti-depressant treatment but future controlled studies are needed to test this hypothesis.

Depression can impair the immunogenicity of vaccine administration in adults. Whereas many vaccinations are administered in childhood, it is not known whether adolescent or adult onset depression is associated with impairments in the maintenance of protection of childhood vaccines. This study tested the hypothesis that individuals with adolescent or adult onset mood disorders would display compromised immunity to measles, a target of childhood vaccination.

IgG antibodies to measles were quantified using a solid phase immunoassay in volunteers with bipolar disorder (BD, n = 64, mean age of onset = 16.6 ± 5.6), currently depressed individuals with major depressive disorder (cMDD, n = 85, mean age of onset = 17.9 ± 7.0), remitted individuals with a history of MDD (rMDD, n = 82, mean age of onset = 19.2 ± 8.6), and non-depressed comparison controls (HC, n = 202), all born after the introduction of the measles vaccine in the USA in 1963.

Relative to HC, both the cMDD group (p = 0.021, adjusted odds ratios (OR) = 0.47, confidence interval (CI) = 0.24–0.90), and the rMDD group (p = 0.038, adjusted OR = 0.50, CI = 0.26–0.97) were less likely to test seropositive for measles. Compared with unmedicated MDD participants, currently medicated MDD participants had a longer lifetime duration of illness and were less likely to test seropositive for measles.

Individuals with adolescent or adult onset MDD are less likely to test seropositive for measles. Because lower IgG titers are associated with increased risk of measles infection, MDD may increase the risk and severity of infection possibly because of impaired maintenance of vaccine-related protection from measles.