The neuroimmunological kynurenine pathway (KP) has been implicated in major depressive disorder (MDD) in adults and adolescents, most recently in suicidality in adults. The KP is initiated by the enzyme indoleamine 2,3-dioxygenase (IDO), which degrades tryptophan (TRP) into kynurenine (KYN) en route to neurotoxins. Here, we examined the KP in 20 suicidal depressed adolescents—composed of past attempters and those who expressed active suicidal intent—30 non-suicidal depressed youth, and 22 healthy controls (HC). Plasma levels of TRP, KYN, 3-hydroxyanthranilic acid, and KYN/TRP (index of IDO) were assessed. Suicidal adolescents showed decreased TRP and elevated KYN/TRP compared to both non-suicidal depressed adolescents and HC. Findings became more significantly pronounced when excluding medicated participants, wherein there was also a significant positive correlation between KYN/TRP and suicidality. Finally, although depressed adolescents with a history of suicide attempt differed from acutely suicidal adolescents with respect to disease severity, anhedonia, and suicidality, the groups did not differ in KP measures. Our findings suggest a possible specific role of the KP in suicidality in depressed adolescents, while illustrating the clinical phenomenon that depressed adolescents with a history of suicide attempt are similar to acutely suicidal youth and are at increased risk for completion of suicide.

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Background There has been growing interest under the Research Domain Criteria initiative to investigate behavioral constructs and their underlying neural circuitry. Abnormalities in reward processes are salient across psychiatric conditions and may precede future psychopathology in youth. However, the neural circuitry underlying such deficits has not been well defined. Therefore, in this pilot, we studied youth with diverse psychiatric symptoms and examined the neural underpinnings of reward anticipation, attainment, and positive prediction error (PPE, unexpected reward gain). Clinically, we focused on anhedonia, known to reflect deficits in reward function. Methods Twenty-two psychotropic medication-free youth, 16 with psychiatric symptoms, exhibiting a full range of anhedonia, were scanned during the Reward Flanker Task. Anhedonia severity was quantified using the Snaith-Hamilton Pleasure Scale. Functional magnetic resonance imaging analyses were false discovery rate corrected for multiple comparisons. Results Anticipation activated a broad network, including the medial frontal cortex and ventral striatum, while attainment activated memory and emotion-related regions such as the hippocampus and parahippocampal gyrus, but not the ventral striatum. PPE activated a right-dominant fronto-temporo-parietal network. Anhedonia was only correlated with activation of the right angular gyrus during anticipation and the left precuneus during PPE at an uncorrected threshold. Limitations Findings are preliminary due to the small sample size. Conclusions This pilot characterized the neural circuitry underlying different aspects of reward processing in youth with diverse psychiatric symptoms. These results highlight the complexity of the neural circuitry underlying reward anticipation, attainment, and PPE. Furthermore, this study underscores the importance of RDoC research in youth.

Background Mitochondrial dysfunction has been increasingly examined as a potential pathogenic event in psychiatric disorders, although its role early in the course of major depressive disorder (MDD) is unclear. Therefore, the purpose of this study was to investigate mitochondrial dysfunction in medication-free adolescents with MDD through in vivo measurements of neurometabolites using high-spatial resolution multislice/multivoxel proton magnetic resonance spectroscopy. Methods Twenty-three adolescents with MDD and 29 healthy controls, ages 12–20, were scanned at 3T and concentrations of ventricular cerebrospinal fluid lactate, as well as N-acetyl-aspartate (NAA), total creatine (tCr), and total choline (tCho) in the bilateral caudate, putamen, and thalamus were reported. Results Adolescents with MDD exhibited increased ventricular lactate compared to healthy controls [F(1, 41) = 6.98, p = .01]. However, there were no group differences in the other neurometabolites. Dimensional analyses in the depressed group showed no relation between any of the neurometabolites and symptomatology, including anhedonia and fatigue. Conclusions Increased ventricular lactate in depressed adolescents suggests mitochondrial dysfunction may be present early in the course of MDD; however it is still not known whether the presence of mitochondrial dysfunction is a trait vulnerability of individuals predisposed to psychopathology or a state feature of the disorder. Therefore, there is a need for larger multimodal studies to clarify these chemical findings in the context of network function.

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Responses to affect include cognitive processes (i.e., perseverative vs. non-perseverative) and valence (i.e., modulation of positive vs. negative affect). However, little research has examined how the factor structure of responses to affect is defined along one or both of these dimensions. The present study conducted an exploratory factor analysis (EFA) of items from assessments of repetitive negative thinking, rumination on positive affect (PA), and dampening. We also examined the associations between emergent factors and measures of depressive symptoms, social anxiety symptoms, and non-social state anxiety. EFA results suggested a three-factor model of repetitive negative thinking, dampening, and rumination on PA. There was a significant association between repetitive negative thinking and dampening factors, but not between other factors. Repetitive negative thinking and dampening were associated with greater internalizing symptoms, whereas rumination on PA was associated with fewer internalizing symptoms. These findings clarify the structure of these responses to affect and their differential associations with symptoms, which may be used to tailor cognitive interventions for anxiety and/or depression.

Objective Findings from prior research on reward sensitivity in nonsuicidal self‐injury (NSSI) have been mixed. Childhood maltreatment is an independent risk factor for NSSI and for hyposensitivity to rewards. This study aimed to disentangle the role of reward sensitivity as a predictor of NSSI for those with an elevated severity of childhood maltreatment. Method In a diverse undergraduate sample (N = 586), trait reward sensitivity (i.e., behavioral approach system subscales) and the severity of maltreatment were assessed as predictors of a lifetime history of NSSI. In a subset of this sample (n = 51), predictors of NSSI urge intensity were measured using ecological momentary assessment. Results Individuals with elevated maltreatment who reported less positive responsiveness to rewards were more likely to have a lifetime history of NSSI. Those with elevated maltreatment who reported a lower likelihood to approach rewards experienced more intense NSSI urges across the ten‐day observation period. However, those with elevated maltreatment who reported a greater likelihood to approach rewards experienced less intense NSSI urges. Conclusions The role of reward sensitivity as a cognitive risk factor for NSSI varies depending on childhood maltreatment history. Findings indicate that, for those with elevated maltreatment, hypersensitivity to approaching rewards may decrease risk for NSSI urges.