Novelty-seeking tendencies in adolescents may promote innovation as well as problematic impulsive behaviour, including drug abuse. Previous research has not clarified whether neural hyper- or hypo-responsiveness to anticipated rewards promotes vulnerability in these individuals. Here we use a longitudinal design to track 144 novelty-seeking adolescents at age 14 and 16 to determine whether neural activity in response to anticipated rewards predicts problematic drug use. We find that diminished BOLD activity in mesolimbic (ventral striatal and midbrain) and prefrontal cortical (dorsolateral prefrontal cortex) regions during reward anticipation at age 14 predicts problematic drug use at age 16. Lower psychometric conscientiousness and steeper discounting of future rewards at age 14 also predicts problematic drug use at age 16, but the neural responses independently predict more variance than psychometric measures. Together, these findings suggest that diminished neural responses to anticipated rewards in novelty-seeking adolescents may increase vulnerability to future problematic drug use.
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It is unclear whether deviations in brain and behavioral development, which may underpin elevated substance use during adolescence, are predispositions for or consequences of substance use initiation. Here, we examine behavioral and neuroimaging indices at early and mid-adolescence in drug-naive youths to identify possible predisposing factors for substance use initiation and its possible consequences. Method: Among 304 drug-naive adolescents at baseline (age 14 years) from the IMAGEN dataset, 83 stayed drug-naive, 133 used alcohol on 1 to 9 occasions, 42 on 10 to 19 occasions, 27 on 20 to 39 occasions, and 19 on >40 occasions at follow-up (age 16 years). Baseline measures included brain activation during the Monetary Incentive Delay task. Data at both baseline and follow-up included measures of trait impulsivity and delay discounting. Results: From baseline to follow-up, impulsivity decreased in the 0 and 1-to 9-occasions groups (p < .004), did not change in the 10-to 19-occasions and 20-to 29-occasions groups (p > .294), and uncharacteristically increased in the >40-occasions group (p ¼ .046). Furthermore, blunted medial orbitofrontal cortex activation during reward outcome at baseline significantly predicted higher alcohol use frequency at follow-up, above and beyond behavioral and clinical variables (p ¼ .008).
Conclusion:These results suggest that the transition from no use to frequent drinking in early to mid-adolescence may disrupt normative developmental changes in behavioral control. In addition, blunted activity of the medial orbitofrontal cortex during reward outcome may underscore a predisposition toward the development of more severe alcohol use in adolescents. This distinction is clinically important, as it informs early intervention efforts in preventing the onset of substance use disorder in adolescents.
A variety of organisms have been shown to have altered physiology or developed pathology as a result of gene transfer, but mammals has never been shown to do so. Here, we show that circulating tumor DNA (ct) can promote cell-specific horizontal gene transfer (HGT) between human cancer cells and explain the mechanisms behind this phenomenon. Once ctDNA enters the host cell, it migrates to the nucleus and integrate into the cells genome, thereby transferring its genetic information. We determine that retrotransposons of the ERVL, SINE, and LINE families are necessary for cell targeting and the integration of ctDNA into host DNA. By using chemically synthesized retrotransposons, we found that AluSp and MER11C reproduced multiple myeloma (MM) ctDNAs cell targeting and integration into MM cells. We also discovered that ctDNA may, as a result of HGT, influence the treatment response of multiple myeloma and pancreatic cancer models. Overall, this is the first study to show that retrotransposon-directed HGT can promote genetic material transfer in cancer. There is, however, a wider impact of our findings than just cancer, since cell free DNA has also been found in physiological and other pathological conditions as well. Furthermore, with the discovery of transposons-mediated tissue specific targeting, a new avenue for the delivery of genes and therapies will emerge.
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