Review
Personality traits and vulnerability or resilience to substance use disorders

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Highlights

  • Clear evidence supports a genetic basis for substance use disorders (SUD)

  • The search to identify individual gene contributions to SUD has been unsuccessful.

  • Three high-order personality traits can be used as endophenotypes for SUD.

  • These personality traits are tied to specific brain systems and genes.

  • These brain systems determine vulnerability or resilience to developing SUD.

Clear evidence supports a genetic basis for substance use disorders (SUD). Yet, the search to identify individual gene contributions to SUD has been unsuccessful. Here, we argue for the study of endophenotypes within the frame of individual differences, and identify three high-order personality traits that are tied to specific brain systems and genes, and that offer a tractable approach to studying SUD. These personality traits, and the genes that moderate them, interact dynamically with the environment and with the drugs themselves to determine ultimately an individual's vulnerability or resilience to developing SUD.

Section snippets

Genes and substance use disorders

Although most people in the general population are exposed to drugs and/or alcohol at some point during their lives, only a small fraction of these individuals develops an unremitting SUD [1]. Informed estimates place lifetime risk of transitioning from drug use to dependence from 8.9% to 67.5% [2] depending on the drug used. Strong evidence suggests an important genetic contribution to the vulnerability to SUD. Epidemiological family and twin studies provide heritability estimates of

Positive emotionality/extraversion and SUD

The positive emotionality/extraversion (PEM/E) personality trait represents an underlying dimension of sensitivity to reward (Box 2). PEM/E is characterized by a state of positive affect, strong motivation, desire, wanting, as well as feelings of being excited, enthusiastic, active, and optimistic. The strongest candidate brain system involved in these affective states is the central dopaminergic system, which originates in the mesencephalon (substantia nigra and ventral tegmental area) and

Negative emotionality/neuroticism and SUD

The negative emotionality/neuroticism (NEM/N) personality trait represents an underlying dimension of sensitivity to signals of punishment (Box 2). Individuals with high NEM/N are more likely to experience feelings such as anxiety, anger, envy, guilt, and depressed mood. They respond more poorly to stressors, being more likely to interpret ordinary situations as threatening and minor frustrations as hopelessly difficult. The bidirectional connections between prefrontal cortex (PFC),

Constraint and SUD

The higher order dimension of constraint (CON) encompasses tendencies toward behavioral restraint versus impulsiveness (Box 2) or, more properly, impulsive action, to distinguish it from impulsive choice (Box 3). CON implies intentional volitional motor control, which can be operationally measured by laboratory tests of response inhibition and task switching [46]. Neuropsychological studies after brain lesions and imaging studies are providing a clear picture of the prefrontal-basal ganglia

Concluding remarks: a new frame to study resilience and vulnerability to SUD

We now appreciate that specific brain circuits modulate well-defined higher-order personality traits, and that these circuits have been inextricably linked to specific gene associations. This heuristic model is based on a continuum of three independent variables (constituted by three main orthogonal personality traits) that interact dynamically and with the environment to determine the degree of vulnerability to the development of SUD. Individuals with low PEM/E, high NEM/N, and low CON would

Acknowledgments

Supported by the NIDA Intramural Research Program.

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