A common genetic network underlies substance use disorders and disruptive or externalizing disorders

Here we summarize evidence obtained by our group during the last two decades, and contrasted it with a review of related data from the available literature to show that behavioral syndromes involving attention deficit/hyperactivity disorder (ADHD), externalizing disorders, and substance-use disorder (SUD) share similar signs and symptoms (i.e., have a biological basis as common syndromes), physiopathological and psychopathological mechanisms, and genetic factors. Furthermore, we will show that the same genetic variants harbored in different genes are associated with different syndromes and that non-linear interactions between genetic variants (epistasis) best explain phenotype severity, long-term outcome, and response to treatment. These data have been depicted in our studies by extended pedigrees, where ADHD, externalizing symptoms, and SUD segregate and co-segregate. Finally, we applied here a new formal network analysis using the set of significantly replicated genes that have been shown to be either associated and/or linked to ADHD, disruptive behaviors, and SUD in order to detect significantly enriched gene categories for protein and genetic interactions, pathways, co-expression, co-localization, and protein domain similarity. We found that networks related to pathways involved in axon guidance, regulation of synaptic transmission, and regulation of transmission of nerve impulse are overrepresented. In summary, we provide compiled evidence of complex networks of genotypes underlying a wide phenotype that involves SUD and externalizing disorders

Adolescent Brain Development and the Risk for Alcohol and Other Drug Problems

Dynamic changes in neurochemistry, fiber architecture, and tissue composition occur in the adolescent brain. The course of these maturational processes is being charted with greater specificity, owing to advances in neuroimaging and indicate grey matter volume reductions and protracted development of white matter in regions known to support complex cognition and behavior. Though fronto-subcortical circuitry development is notable during adolescence, asynchronous maturation of prefrontal and limbic systems may render youth more vulnerable to risky behaviors such as substance use. Indeed, binge-pattern alcohol consumption and comorbid marijuana use are common among adolescents, and are associated with neural consequences. This review summarizes the unique characteristics of adolescent brain development, particularly aspects that predispose individuals to reward seeking and risky choices during this phase of life, and discusses the influence of substance use on neuromaturation. Together, findings in this arena underscore the importance of refined research and programming efforts in adolescent health and interventional needs

TRH response pattern in adolescent schizophrenic males.

A marked elevation in human growth hormone (GH) following intravenous infusion of thyrotropin releasing hormone (TRH) was seen in three of seven adolescent male schizophrenic patients receiving neuroleptic drugs, and in one of five controls matched for age, sex, and developmental stage, receiving the same drugs. A positive family history for schizophrenia was noted in all three schizophrenic \u27responders\u27 but in only one of the remaining patients. The response patterns of thyroid stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) following TRH infusion were not significantly different in the two groups. No significant correlations were found between T3, T4, TSH, or GH response patterns and age of patient, duration of illness, medication dose or duration, weight change, or hours of sleep preceding testing

Cardiovascular risk and occupation.

ABSTRACT

Extremely low frequency magnetic field promotes differentiation of the ex vivo expanded human cardiac stem cells

Exposure to extremely low frequency magnetic field can modulates the cardiogenic versus angiogenic differentiation process of ex vivo expanded CSC