No abstract

These findings suggest that deficits in fear regulation, rather than in the excitatory response itself, are more critical to the pathophysiology of GAD in the context of fear generalization.

An inverse relationship between regional change in use of antidepressants and suicide raises the possibility of a role for using antidepressant treatment in youth suicide prevention efforts, especially for males, older adolescents, and adolescents who reside in lower-income regions.

The ventromedial prefrontal cortex (vmPFC) plays a critical role in a number of evaluative processes, including risk assessment. Impaired discrimination between threat and safety is considered a hallmark of clinical anxiety. Here, we investigated the circuit-wide structural and functional mechanisms underlying vmPFC threat-safety assessment in humans. We tested patients with generalized anxiety disorder (GAD; n ϭ 32, female) and healthy controls (n ϭ 25, age-matched female) on a task that assessed the generalization of conditioned threat during fMRI scanning. The task consisted of seven rectangles of graded widths presented on a screen; only the midsize one was paired with mild electric shock [conditioned stimulus (CS)], while the others, safety cues, systematically varied in width by Ϯ20, 40, and 60% [generalization stimuli (GS)] compared with the CS. We derived an index reflecting vmPFC functioning from the BOLD reactivity on a continuum of threat (CS) to safety (GS least similar to CS); patients with GAD showed less discrimination between threat and safety cues, compared with healthy controls (Greenberg et al., 2013b). Using structural, functional (i.e., resting-state), and diffusion MRI, we measured vmPFC thickness, vmPFC functional connectivity, and vmPFC structural connectivity within the corticolimbic systems. The results demonstrate that all three factors predict individual variability of vmPFC threat assessment in an independent fashion. Moreover, these neural features are also linked to GAD, most likely via an vmPFC fear generalization. Our results strongly suggest that vmPFC threat processing is closely associated with broader corticolimbic circuit anomalies, which may synergistically contribute to clinical anxiety.

Anticipation is a central component of anxiety and the anterior insula appears to be an important neural substrate in which this process is mediated. The anterior insula is also thought to underlie the interoceptive representation of one's affective state. However, the degree to which individual differences in anticipation-related insula reactivity are associated with variability in the subjective experience of anxious anticipation is untested. To assess this possibility, functional magnetic resonance images were acquired while participants completed an auditory anticipation task with trial-by-trial self-report ratings of anxious anticipation. We hypothesized that the anterior insula would be positively associated with an individual's subjective experience of anticipatory anxiety. The results provide evidence for an amygdalo-insular system involved in anxious auditory anticipation. Reactivity in the right anterior insula was predictive of individuals' subjective experience of anxious anticipation for both aversive and neutral stimuli, whereas the amygdala was predictive of anticipatory anxiety for aversive stimuli. In addition, anxious anticipatory activation in the left insula and left amygdala covaried with participants' level of trait anxiety, particularly when the anticipated event was proximal.

Mental disorders are diagnosed in roughly one half of emergency department visits by young people following an episode of deliberate self-harm. Systematic mental health assessments in the emergency department of young people following an episode of deliberate self-harm may improve detection of mental disorders.

No abstract

Objective Anhedonia, disrupted reward processing, is a core symptom of major depressive disorder. Recent findings demonstrate altered reward-related ventral striatal reactivity in depressed individuals, but the extent to which this is specific to anhedonia remains poorly understood. The authors examined the effect of anhedonia on reward expectancy (expected outcome value) and prediction error-(discrepancy between expected and actual outcome) related ventral striatal reactivity, as well as the relationship between these measures. Method A total of 148 unmedicated individuals with major depressive disorder and 31 healthy comparison individuals recruited for the multisite EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care) study underwent functional MRI during a well-validated reward task. Region of interest and whole-brain data were examined in the first- (N=78) and second- (N=70) recruited cohorts, as well as the total sample, of depressed individuals, and in healthy individuals. Results Healthy, but not depressed, individuals showed a significant inverse relationship between reward expectancy and prediction error-related right ventral striatal reactivity. Across all participants, and in depressed individuals only, greater anhedonia severity was associated with a reduced reward expectancy-prediction error inverse relationship, even after controlling for other symptoms. Conclusions The normal reward expectancy and prediction error-related ventral striatal reactivity inverse relationship concords with conditioning models, predicting a shift in ventral striatal responding from reward outcomes to reward cues. This study shows, for the first time, an absence of this relationship in two cohorts of unmedicated depressed individuals and a moderation of this relationship by anhedonia, suggesting reduced reward-contingency learning with greater anhedonia. These findings help elucidate neural mechanisms of anhedonia, as a step toward identifying potential biosignatures of treatment response.