Purpose of Review Studies of the neurobiology and treatment of PTSD have highlighted many aspects of the pathophysiology of this disorder that might be relevant to treatment. The purpose of this review is to highlight the potential clinical importance of an often-neglected consequence of stress models in animals that may be relevant to PTSD: the stress-related loss of synaptic connectivity. Recent Findings Here, we will briefly review evidence that PTSD might be a “synaptic disconnection syndrome” and highlight the importance of this perspective for the emerging therapeutic application of ketamine as a potential rapid-acting treatment for this disorder that may work, in part, by restoring synaptic connectivity. Summary Synaptic disconnection may contribute to the profile of PTSD symptoms that may be targeted by novel pharmacotherapeutics.

Imminent suicide is difficult to predict. Suicide usually occurs on the first attempt. Suicide may consist of suicidal crises, with fluctuating and unpredictable risk, superimposed on long-term latent susceptibility. Risk characteristics are consistent with interacting long-term (sensitization) and short-term (impulsivity) mechanisms: sensitization to stress/trauma perceived as inescapable, or to addiction, can increase latent action-impulsivity, disinhibiting high-risk behavior including suicidal ideation and aggression. Survived medically severe suicide attempts are associated with severe morbidity and premature death. Therefore, it is necessary to identify characteristics that may predict a first attempt. We used Bayesian logistic regression and path analysis to identify direct and indirect (via suicidal ideation-worst (SSI-W)) predictors of MSSA in 28 adult survivors of MSSA and 23 symptomatically and demographically similar non-attempters (NA). SSI-W increased odds ratio (OR) for MSSA; Cumulative Adversity and action-impulsivity increased OR for MSSA independent of SSI-W. SSI-W mediated increased MSSA by aggression, alcohol use, and depression. Childhood Trauma Minimization/Denial increased MSSA directly but correlated negatively with SSI-W. MSSA required latent aggression or impulsivity combined with stress-sensitization and increased action-impulsivity. These interacting characteristics are potential targets for identification and preventive treatment of risk for suicide regardless of attempt history.

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