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Objective: Substance use disorder (SUD) is a major public health crisis, with increased overdose deaths in the past decade. This has coincided with a tremendous amount of research on those who misuse substances. However, extensive research on SUD vulnerability characteristics such as impulsivity may be complemented by research on theoretically relevant aspects of cognition. The Cognitive Reflection Test (CRT) was designed to measure a person’s ability to subdue quick, intuitive decisions to reflect or deliberate. To some decision making theorists, this measure may help explain why some people are better able to inhibit “gut reactions” than others. Methods: We recruited 140 veterans from a Veterans Affairs medical center; 91 of whom were receiving SUD treatment. Participants completed the CRT and a measure of trait impulsivity (the UPPS-P). We ran planned ANCOVAs assessing differences in the number of correct answers on the CRT and the proportion of errors that were intuitive. Results: Participants who were receiving treatment gave significantly fewer correct, reflective answers on the CRT compared to controls. However, there were no significant differences in the proportion of errors that were due to intuitive responses. These findings did not change when controlling for age and/or trait impulsivity. Conclusion: Those suffering from SUD may exhibit cognitive deficits that do not stem from intuitive thinking. These deficits may, in turn, exacerbate issues arising from elevated impulsivity. Additional research which better incorporates decision making theory may be invaluable in providing clinically-relevant results and positive public health outcomes.

IMPORTANCE: Selecting effective antidepressants for the treatment of major depressive disorder (MDD) is an imprecise practice, with remission rates of about 30% at the initial treatment. OBJECTIVE: To determine whether pharmacogenomic testing affects antidepressant medication selection and whether such testing leads to better clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS: A pragmatic, randomized clinical trial that compared treatment guided by pharmacogenomic testing vs usual care. Participants included 676 clinicians and 1944 patients. Participants were enrolled from 22 Department of Veterans Affairs medical centers from July 2017 through February 2021, with follow-up ending November 2021. Eligible patients were those with MDD who were initiating or switching treatment with a single antidepressant. Exclusion criteria included an active substance use disorder, mania, psychosis, or concurrent treatment with a specified list of medications. INTERVENTIONS: Results from a commercial pharmacogenomic test were given to clinicians in the pharmacogenomic-guided group (n = 966). The comparison group received usual care and access to pharmacogenomic results after 24 weeks (n = 978). MAIN OUTCOMES AND MEASURES: The co–primary outcomes were the proportion of prescriptions with a predicted drug-gene interaction written in the 30 days after randomization and remission of depressive symptoms as measured by the Patient Health Questionnaire–9 (PHQ-9) (remission was defined as PHQ-9 ≤ 5). Remission was analyzed as a repeated measure across 24 weeks by blinded raters. RESULTS: Among 1944 patients who were randomized (mean age, 48 years; 491 women [25%]), 1541 (79%) completed the 24-week assessment. The estimated risks for receiving an antidepressant with none, moderate, and substantial drug-gene interactions for the pharmacogenomic-guided group were 59.3%, 30.0%, and 10.7% compared with 25.7%, 54.6%, and 19.7% in the usual care group. The pharmacogenomic-guided group was more likely to receive a medication with a lower potential drug-gene interaction for no drug-gene vs moderate/substantial interaction (odds ratio [OR], 4.32 [95% CI, 3.47 to 5.39]; P

OBJECTIVE: To determine if elevated rapid-response impulsivity following blast exposure (as a putative marker of ventral prefrontal cortex (vPFC) damage) is predictive of future elevated affective symptomatology in blast-exposed service members. DESIGN: Longitudinal design with neurocognitive testing at initial assessment and one-year follow-up assessment of psychiatric symptomatology by telephone interview. SETTING: Veterans Administration medical centers and post-deployment assessment centers at military bases. PARTICIPANTS: Blast-exposed US military personnel (N=84) age 19–39. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Center for Epidemiological Studies-Depression Scale (CES-D) scores, post-traumatic stress disorder (PTSD) checklist (PCL-5) scores, and Alcohol Use Disorders Identification Test-C (AUDIT-C) scores at the 12-month follow-up telephone interview. RESULTS: After controlling for age and affective symptom scores reported at initial assessment, commission errors on the Continuous Performance Test-II of the initial assessment were predictive of higher symptom scores in CES-D and PCL-5 at follow-up, but were not predictive of AUDIT-C scores. CONCLUSION: Elevated rapid-response impulsivity, as a behavioral marker of reduced top-down frontocortical control, is a risk factor for elevated mood and PTSD symptoms over time in blast-exposed individuals. Future longitudinal studies with pre-deployment neurobehavioral testing could enable attribution of this relationship to blast-related vPFC damage.