Addictions constitute the most costly medical illnesses in society today. Onset of drug addiction often beginsin adolescence and an improved understanding of the neural correlates of addiction vulnerability within thisdevelopmental period has significant implications for prevention and treatment interventions. Few priorinvestigations have followed at-risk cohorts from birth through adolescence, and many have focused onboys, generating a relative deficiency in our understanding of these processes in girls and in how boys andgirls differ. No longitudinal studies to date have used brain imaging to identify how boys and girls at risk foraddiction differ in brain function. Furthermore, although cocaine and other drug exposure in utero remains asignificant public health problem, no studies to date have examined the influence of such exposure uponhuman adolescent brain function or addiction vulnerability. We propose examining 120 adolescent girls andboys 13-15 years of age who have been followed since birth, and were either prenatally cocaine-exposed to(PCE) or non-drug exposed in utero (NDE) and are matched on important sociodemographic features thatcategorize them as particularly vulnerable to the development of addiction. We propose using fMRI toinvestigate gender differences in the neural correlates of stress-responsiveness using an fMRI paradigm thatour group has developed and used in prior SCOR-supported research. Our prior SCOR research found thatadult men and women differed in the neural responses to individualized stress, appetitive and neutral scriptswithin limbic or 'emotion-related' brain regions including caudate, amygdala, hippocampus and anteriorcingulate, and that these differences in activations were largely observed during the stress scripts.Furthermore, these responses were differentially altered by chronic cocaine abuse in men and women. Wepropose using this paradigm to examine: 1) sex differences in the neural correlates of stress-responses inthese younger individuals at increased risk for addiction; 2) sex differences in neural activations related to in-utero cocaine exposure; and, 3) the stress-related brain activity that is predictive of subsequent substanceuse behaviors in girls and boys and how they differ across sex group. Findings from this study will providecritical gender-specific data on brain correlates of stress responses in adolescent girls and boys and provideinsights into the risk related neural pathways in adolescent addiction.
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| Milivojevic, Verica; Fox, Helen C; Jayaram-Lindstrom, Nitya et al. (2017) Sex differences in guanfacine effects on stress-induced stroop performance in cocaine dependence. Drug Alcohol Depend 179:275-279 |
| Morie, Kristen P; Yip, Sarah W; Zhai, Zu Wei et al. (2017) White-matter crossing-fiber microstructure in adolescents prenatally exposed to cocaine. Drug Alcohol Depend 174:23-29 |
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| Zakiniaeiz, Yasmin; Yip, Sarah W; Balodis, Iris M et al. (2017) Altered functional connectivity to stressful stimuli in prenatally cocaine-exposed adolescents. Drug Alcohol Depend 180:129-136 |
| Milivojevic, Verica; Fox, Helen C; Sofuoglu, Mehmet et al. (2016) Effects of progesterone stimulated allopregnanolone on craving and stress response in cocaine dependent men and women. Psychoneuroendocrinology 65:44-53 |
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