Glutamate-hypothalamic-pituitary-adrenal axis interactions: implications for mood and anxiety disorders

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is a pathologic feature of certain mood and anxiety disorders that results in the increased production and secretion of corticotropin-releasing factor. There is increasing preclinical evidence that glutamate, an excitatory amino acid, plays an important role in the regulation of the HPA axis. Activation of glutamatergic projections to limbic structures such as the amygdala and brainstem structures such as the nucleus tractus solitarius is implicated in the stress response. There are laboratory and clinical suggestions that glutamatergic N-methyl-D-aspartate (NMDA) receptor antagonists function as antidepressants, and that chronic antidepressant treatments have a significant impact on NMDA receptor function. Clinical investigations of glutamate antagonists in patients with mood and anxiety disorders are in their infancy, with a few reports suggesting the presence of mood-elevating properties. Ultimately, HPA axis modulators, serotonin-enhancing agents, and glutamate antagonists might serve to increase neurotropic factors in key brain regions for affective and anxiety regulation, providing a putative final common pathway.     

Doing Science,Technology and Society in the National Science Foundation

The author describes his efforts to become a participant observer while he was a Program Director at the NSF. He describes his plans for keeping track of his reflections and his goals before he arrived at NSF, then includes sections from his reflective diary and comments after he had completed his two-year rotation. The influx of rotators means the NSF has to be an adaptive, learning organization but there are bureaucratic obstacles in the way.     

Predicting Persistence of Nonsuicidal Self‐Injury in Suicidal Adolescents

Prospective predictors of persistent nonsuicidal self‐injury (NSSI) were examined in adolescents admitted to an inpatient psychiatric unit for suicidal behaviors and followed naturalistically for 6 months. Seventy‐one (77%) participants reported NSSI at baseline, and 40 (56%) persisted at the 6 month follow‐up. Those who endorsed automatic positive reinforcement (APR) as the predominant reason for NSSI were more likely to persist in NSSI. Depression over follow‐up, but not at baseline, also predicted persistence. These results suggest that helping high‐risk adolescents to identify alternative ways of generating emotion(s) to counter the effects of APR that may accompany NSSI should be a high priority treatment target.     

The Suicidal Narrative and Its Relationship to the Suicide Crisis Syndrome and Recent Suicidal Behavior

In this study, we introduce the construct of the suicidal narrative, a hypothetical personal narrative linked to imminent suicide, and explore its relationship to near‐term suicidal risk and the suicide crisis syndrome (SCS). Psychiatric outpatients (N = 289) were administered the Columbia Suicide‐Severity Rating Scale (C‐SSRS), Suicide Crisis Inventory (SCI), and Suicide Narrative Inventory (SNI), a novel instrument combining the documented risk factors of Thwarted Belongingness, Perceived Burdensomeness, Humiliation, Social Defeat, Goal Disengagement, and Goal Reengagement. Dimensional measures of past month, lifetime, and past suicidal phenomena, incorporating ideation and behavior, were calculated from the C‐SSRS. Structural equation modeling was used to explore the interaction among variables. Factor analysis of the SNI yielded two orthogonal factors, termed Interpersonal and Goal Orientation. The former factor was comprised of Perceived Burdensomeness, Social Defeat, Humiliation, and Thwarted Belongingness, the latter of Goal Disengagement and Goal Reengagement. The Interpersonal factor correlated with both SCS severity and suicidal phenomena in each time frame and the Goal Orientation factor with no other variable. As hypothesized, the proposed model was significant for the past month only. Our findings support the construct of the suicidal narrative and its function as a near‐term suicidal risk factor.     

I Can Stomach That! Fearlessness About Death Predicts Attenuated Facial Electromyography Activity in Response to Death‐Related Images

Objective measures of suicide risk can convey life‐saving information to clinicians, but few such measures exist. This study examined an objective measure of fearlessness about death (FAD), testing whether FAD relates to self‐reported and physiological aversion to death. Females (n = 87) reported FAD and disgust sensitivity, and facial electromyography was used to measure physiological facial responses consistent with disgust while viewing death‐related images. FAD predicted attenuated expression of physiological death aversion, even when controlling for self‐reported death‐related disgust sensitivity. Diminished physiological aversion to death‐related stimuli holds promise as an objective measure of FAD and suicide risk.     

Positive and Negative Expectations of Hopelessness as Longitudinal Predictors of Depression,Suicidal Ideation,and Suicidal Behavior in High‐Risk Adolescents

The relationship between hopelessness and depression in predicting suicide‐related outcomes varies based on the anticipation of positive versus negative events. In this prospective study of adolescents at elevated risk for suicide, we used two Beck Hopelessness Scale subscales to assess the impact of positive and negative expectations in predicting depression, suicidal ideation, and suicidal behavior over a 2‐ to 4‐year period. In multivariate regressions controlling for depression, suicidal ideation, and negative‐expectation hopelessness, positive‐expectation hopelessness was the only significant predictor of depressive symptoms and suicidal behavior. Clinical interventions may benefit from bolstering positive expectations and building optimism.