Impaired self-awareness of illness severity (insight) is associated with increased morbidity and poorer treatment outcome across multiple neuropsychiatric diseases. Although the study of insight has traditionally been limited to psychotic disorders (e.g., schizophrenia, mania), emerging theory and evidence suggest that this construct may also be highly relevant to drug addiction. In particular, addicted individuals often overestimate their addiction-related self-control, underestimate their neurocognitive impairments, and fail to seek treatment when it is warranted. In this R21 application, we provide the first direct investigation of insight impairment in drug addiction and its underlying neurobiology. Individuals with cocaine use disorder (CUD) and matched healthy controls (HC) will complete a brand-new functional magnetic resonance imaging (fMRI) insight task, during which they will respond to probes about the severity of their drug use.
Specific Aims i nclude uncovering the behavioral and neural correlates (both task and baseline resting-state) of impaired insight in CUD, and then validating this task via measures of social-cognitive functioning (self-awareness and emotional awareness) and drug use. We hypothesize that this fMRI insight task will identify a subpopulation of CUD with impaired insight into their addiction severity, which in these individuals will be associated with focal- and network-related deficits of the rostral anterior cingulate cortex extending into the ventromedial prefrontal cortex (rACC/vmPFC). This region, insofar as it mediates personal relevance and is disrupted in addiction and other psychopathologies, indeed provides a plausible candidate region for studying insight. We further hypothesize that this insight impairment and its underlying functional deficits will correlate with reduced social-cognitive functioning and increased drug use. Taken together, in this project we map a newly appreciated addiction- related symptom (insight) onto functional deficits of corticolimbic circuitry that mediate self-related processing. This approach can then be applied to other diseases of impaired insight (e.g., schizophrenia, mania), with the goal of identifying a common thread (insight) that links drug addiction with these other disorders. Even more broadly, studying impaired insight vis--vis general abnormalities of core social-cognitive functioning (i.e., tagging behavior and emotions with personal relevance and emotional salience in association with rACC/vmPFC function) could even help illuminate the basic science of social-cognitive processing in health.

Public Health Relevance

This research will uncover for the first time the direct neural correlates of compromised insight in human drug addiction, helping to elucidate why so many addicted individuals fail to recognize the need for treatment despite the pervasive consequences of chronic drug use. This research can also lay the foundation for future clinical intervention studies in addiction that endeavor to enhance insight to improve treatment outcome, with possible application to other neuropsychiatric diseases of impaired insight as well.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DA040046-01
Application #
8948519
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Grant, Steven J
Project Start
2015-09-30
Project End
2017-08-31
Budget Start
2015-09-30
Budget End
2016-08-31
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Psychiatry
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Moeller, Scott J; Paulus, Martin P (2018) Toward biomarkers of the addicted human brain: Using neuroimaging to predict relapse and sustained abstinence in substance use disorder. Prog Neuropsychopharmacol Biol Psychiatry 80:143-154
Moeller, Scott J; Zilverstand, Anna; Konova, Anna B et al. (2018) Neural Correlates of Drug-Biased Choice in Currently Using and Abstinent Individuals With Cocaine Use Disorder. Biol Psychiatry Cogn Neurosci Neuroimaging 3:485-494
Huang, Anna S; Mitchell, Jameson A; Haber, Suzanne N et al. (2018) The thalamus in drug addiction: from rodents to humans. Philos Trans R Soc Lond B Biol Sci 373:
Parvaz, Muhammad A; Moeller, Scott J; Goldstein, Rita Z (2016) Incubation of Cue-Induced Craving in Adults Addicted to Cocaine Measured by Electroencephalography. JAMA Psychiatry 73:1127-1134
Moeller, Scott J; Fleming, Stephen M; Gan, Gabriela et al. (2016) Metacognitive impairment in active cocaine use disorder is associated with individual differences in brain structure. Eur Neuropsychopharmacol 26:653-62
Moeller, Scott J; London, Edythe D; Northoff, Georg (2016) Neuroimaging markers of glutamatergic and GABAergic systems in drug addiction: Relationships to resting-state functional connectivity. Neurosci Biobehav Rev 61:35-52
Moeller, Scott J; Stoops, William W (2015) Cocaine choice procedures in animals, humans, and treatment-seekers: Can we bridge the divide? Pharmacol Biochem Behav 138:133-41