Browsing by Subject "Externalizing"

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    Cortical Activation Deficits During Facial Emotion Processing in Youth at High Risk for the Development of Substance Use Disorders
    (Elsevier, 2013) Hulvershorn, Leslie A.; Finn, Peter; Hummer, Tom A.; Leibenluft, Ellen; Ball, Brandon; Gichina, Victoria; Anand, Amit; Psychiatry, School of Medicine
    Background: Recent longitudinal studies demonstrate that addiction risk may be influenced by a cognitive, affective and behavioral phenotype that emerges during childhood. Relatively little research has focused on the affective or emotional risk components of this high-risk phenotype, including the relevant neurobiology. Methods: Non-substance abusing youth (N=19; mean age=12.2) with externalizing psychopathology and paternal history of a substance use disorder and demographically matched healthy comparisons (N=18; mean age=11.9) were tested on a facial emotion matching task during functional MRI. This task involved matching faces by emotions (angry, anxious) or matching shape orientation. Results: High-risk youth exhibited increased medial prefrontal, precuneus and occipital cortex activation compared to the healthy comparison group during the face matching condition, relative to the control shape condition. The occipital activation correlated positively with parent-rated emotion regulation impairments in the high-risk group. Conclusions: These findings suggest a preexisting abnormality in cortical activation in response to facial emotion matching in youth at high risk for the development of problem drug or alcohol use. These cortical deficits may underlie impaired affective processing and regulation, which in turn may contribute to escalating drug use in adolescence.
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    How Phenotype and Developmental Stage Affect the Genes We Find: GABRA2 and Impulsivity
    (Cambridge University Press, 2013) Dick, Danielle M.; Aliev, Fazil; Latendresse, Shawn; Porjesz, Bernice; Schuckit, Marc; Rangaswamy, Madhavi; Hesselbrock, Victor; Edenberg, Howard; Nurnberger, John, Jr.; Agrawal, Arpana; Bierut, Laura; Wang, Jen; Bucholz, Kathy; Kuperman, Samuel; Kramer, John; Biochemistry and Molecular Biology, School of Medicine
    Context: The detection and replication of genes involved in psychiatric outcome has been notoriously difficult. Phenotypic measurement has been offered as one explanation, although most of this discussion has focused on problems with binary diagnoses. Objective: This article focuses on two additional components of phenotypic measurement that deserve further consideration in evaluating genetic associations: (1) the measure used to reflect the outcome of interest, and (2) the developmental stage of the study population. We focus our discussion of these issues around the construct of impulsivity and externalizing disorders, and the association of these measures with a specific gene, GABRA2. Design, setting, and participants: Data were analyzed from the Collaborative Study on the Genetics of Alcoholism Phase IV assessment of adolescents and young adults (ages 12-26; N = 2,128). Main outcome measures: Alcohol dependence, illicit drug dependence, childhood conduct disorder, and adult antisocial personality disorder symptoms were measured by psychiatric interview; Achenbach youth/adult self-report externalizing scale; Zuckerman Sensation-Seeking scale; Barratt Impulsivity scale; NEO extraversion and consciousness. Results: GABRA2 was associated with subclinical levels of externalizing behavior as measured by the Achenbach in both the adolescent and young adult samples. Contrary to previous associations in adult samples, it was not associated with clinical-level DSM symptom counts of any externalizing disorders in these younger samples. There was also association with sensation-seeking and extraversion, but only in the adolescent sample. There was no association with the Barratt impulsivity scale or conscientiousness. Conclusions: Our results suggest that the pathway by which GABRA2 initially confers risk for eventual alcohol problems begins with a predisposition to sensation-seeking early in adolescence. The findings support the heterogeneous nature of impulsivity and demonstrate that both the measure used to assess a construct of interest and the age of the participants can have profound implications for the detection of genetic associations.