Social zeitgeber and sleep loss as risk factors for suicide in American Indian adolescents.

American Indians / Alaska Natives (AI/AN) bear a high burden of suicide, the reasons for which are not completely understood, and rates can vary by tribal group and location. This article aims to identify circumstances reported by a community group of American Indian adolescent participants to be associated with their depression and/or suicide. American Indian adolescents (n = 360) were recruited from contiguous reservations and were assessed with a semi-structured diagnostic interview. Twenty percent of the adolescents reported suicidal thoughts (ideation, plans), an additional 8% reported a history of suicide attempts, and three deaths due to suicide were reported. Suicidal behaviors and major depressive disorder (MDD) co-occurred and were more common among female adolescents. The distressing events that adolescents most often reported were: death in the family, family disruption, peer relationship problems, and school problems. All of these events were significantly associated with suicidal behaviors, however those with suicidal acts were more likely to report death in the family. Those with MDD but no suicidal behaviors were more likely to report disruptions in the family. Disruptions in falling asleep were also associated with suicidal behaviors and having experienced a death in the family. Disruptions in important relationships, particularly through death or divorce, may be interpreted as a loss or disruption in "social zeitgebers" that may in turn disturb biological rhythms, such as sleep, thus potentially increase the risk for MDD and/or suicide. Prevention programs aimed at ameliorating the impact of disruptions in important relationships may potentially reduce suicidal behaviors in AI/AN adolescents.

CNS penetration of small molecules following local inflammation, widespread systemic inflammation or direct injury to the nervous system.

AIMS: We sought to investigate effects of local and systemic inflammation on CNS permeability of small molecules and compare these to effects of direct injury to the nervous system. MAIN METHODS: Evans blue was used to determine the integrity of the blood-brain barrier (BBB) following local inflammation, systemic inflammation, injury to the L5 spinal nerve or transient occlusion of the middle cerebral artery. In addition, three compounds having low, medium and high brain permeability (atenolol, morphine and oxycodone, respectively) were used. Following model establishment (4-hr post-carrageenan, 24-hr post-FCA, 2-, 4- and 24-hr post-LPS, 21 days post-nerve injury) compounds were administered and 30 min later the brain, spinal cord and blood removed. The plasma and tissue concentrations of compounds were quantified by LC/MS/MS. KEY FINDINGS: Localized inflammation did not affect Evans blue penetration into the CNS but significantly increased morphine penetration into the spinal cord. Systemic inflammation increased the quantity of Evans blue in the CNS but also decreased the penetration of atenolol, morphine and oxycodone into the brain 4-hr post-insult. Nerve injury had no effect on Evans blue or compound penetration, while middle cerebral artery occlusion resulted in a large but short lived increase in Evans blue penetration into both the cortex and striatum. SIGNIFICANCE: The presence of inflammation may affect the CNS penetration of some compounds but is unlikely to lead to a large non-selective BBB breakdown. As a result, it is appropriate to test for side-effects, and conduct brain pharmacokinetic determinations, in naïve rats.