Risk for Substance Use Disorders in young adulthood: Associations with developmental experiences of homelessness, foster care, and adverse childhood experiences.

BACKGROUND: Multiple developmental risk factors for Substance Use Disorders (SUDs) during young adulthood have been identified. In this investigation, we examined the impact of homelessness, foster care, and adverse childhood experiences (ACEs) prior to 12th grade on the development of three common SUDs during young adulthood-Alcohol Use Disorder (AUD), Tobacco Use Disorder (TUD) and Cannabis Use Disorder (CUD). Our hypothesis was that while both homelessness and ACEs are significant risk factors for young adult SUDs, foster care involvement might convey protection. METHODS: Using nationally representative data from the National Longitudinal Study of Adolescent to Adult Health, measures of ACEs were derived from the CDC-Kaiser ACE study, and DSM-V SUD diagnoses were derived from items originally based on DSM-IV. SUD diagnoses were binned into "mild", "moderate", and "severe" groupings. Survey-based logistic models were used to estimate risks of SUDs while controlling for demographics. RESULTS: The results suggest that the experience of homelessness prior to 12th grade in addition to ACEs were significantly associated with the development in young adulthood of the most severe forms of AUD and TUD and all severity levels of CUD. Foster care was not associated with either risk or protection from SUDs. CONCLUSIONS: The experience of homelessness during development may be viewed as another detrimental ACE that is a risk factor for the most common SUDs in young adulthood. Given the magnitude of the current epidemic of homelessness in the U.S., these results should raise substantial concern.

Hepatitis C Screening Rate Among Underserved Adults With Serious Mental Illness Receiving Care in California Community Mental Health Centers.

Although HCV is more prevalent among people with severe mental illness (SMI; e.g., schizophrenia, bipolar disorder) than in the general population (17% vs 1%), no large previous studies have examined HCV screening in this population. In this cross-sectional study, we examined administrative data for 57 170 California Medicaid enrollees with SMI to identify prevalence and predictors of HCV screening from October 2010 through September 2011. Only 4.7% (2674 of 57 170) received HCV screening, with strongest predictors being nonpsychiatric health care utilization and comorbid substance abuse.

Basal LAT-diacylglycerol-RasGRP1 signals in T cells maintain TCRα gene expression.

In contrast to the well-characterized T cell receptor (TCR) signaling pathways that induce genes that drive T cell development or polarization of naïve CD4 T cells into the diverse T(H)1, T(H)2, T(H)17 and T(reg) lineages, it is unclear what signals maintain specific gene expression in mature resting T cells. Resting T cells residing in peripheral lymphoid organs exhibit low-level constitutive signaling. Whereas tonic signals in B cells are known to be critical for survival, the roles of tonic signals in peripheral T cells are unknown. Here we demonstrate that constitutive signals in Jurkat T cell lines are transduced via the adapter molecule LAT and the Ras exchange factor RasGRP1 to maintain expression of TCRα mRNA and surface expression of the TCR/CD3 complex. Independent approaches of reducing basal activity through the LAT-diacylglycerol-RasGRP pathway led to reduced constitutive Ras-MEK-ERK signals and decreased TCRα mRNA and surface TCR expression in Jurkat cells. However, loss of TCR expression takes several days in these cell line experiments. In agreement with these in vitro approaches, inducible deletion of Lat in vivo results in reduced TCRα mRNA- and surface TCR-expression in a delayed temporal manner as well. Lastly, we demonstrate that loss of basal LAT-RasGRP signals appears to lead to silencing or repression of TCRα transcription. We postulate that basal LAT-diacylglycerol-RasGRP signals fulfill a regulatory function in peripheral T lymphocytes by maintaining proper gene expression programs.