Hero

Videos

Slideshows

Articles

Podcasts

Poll

Precision medicine took another step forward as Adial Pharmaceuticals announced their intent to enter the genetic testing market. The news comes after the company received a Notice of Allowance from the US Patent and Trademark Office related to use of their genetic diagnostic panel in combination with their lead product, 

“This new patent related to the use of our genetic diagnostic panel in combination with AD04 for the treatment of AUD and OUD is a major milestone as we believe genetic evaluation of patients can be used to identify individuals that may benefit from AD04. We have been utilizing the genetic panel covered by this patent in our ongoing ONWARD™ Phase 3 trial, and, given this patent allowance, we anticipate that genetic diagnostics are expected to be an important segment of our commercial strategy going forward,” Adial’s CEO, William Stilley, said in a statement to the press. “Our view that AUD has a solid nexus in genetics is fundamental to the premise of the successful Phase 2B trial of AD04 conducted at the University of Virginia and our ONWARD™ Phase 3 trial of AD04 currently underway in Europe. And, it is consistent with Adial’s premise that the presence of certain genetics is expected to substantially influence whether an individual suffering from AUD or OUD would likely respond to treatment with AD04.”

 is a genetically targeted therapeutic agent for the treatment of AUD. The drug is designed to reduce cravings thereby reducing alcohol intake. patients curb their drinking. The oral medication will not require abstinence before or during treatment. To date, it has shown positive safety and tolerability profiles.

Once issued, the patent is anticipated to provide market exclusivity for the AD04 genetic diagnostic test. With this in mind, Adial plans to enter the genetic testing market as a stand-alone commercial business line and market the genetic diagnostic panel as a Companion Diagnostic Test to AD04. Approximately one-third (33%) of AUD patients are expected to respond to treatment with AD04.

In addition to the benefits for patients, the resulting efficacy may also realize cost savings to the health care industry. “Market research conducted by Adial indicates a willingness among payors to reimburse a genetic companion diagnostic test, and this may allow Adial to provide patients personalized, precision medicine and also potentially provide dramatic cost savings to payors,” Stilley said further.

1. Adial Pharmaceuticals. Adial Pharmaceuticals plans to enter genetic testing market following allowance of US Patent for genetic diagnostic test. News release. June 22, 2021. Accessed June 22, 2021. 

https://ir.adialpharma.com/press-releases/detail/122/adial-pharmaceuticals-plans-to-enter-genetic-testing-market

2. Adial Pharmaceuticals. Technology. Accessed June 22, 2021. 

Adial’s AD04 for the treatment of alcohol use disorder received a Notice of Allowance from the US Patent and Trademark Office. 

Patent Brings Psychiatry One Step Closer to Precision Medicine

The Acting Administrator of the Drug Enforcement Administration has removed samidorphan (3-carboxamido-4-hydroxy naltrexone) and its salts from the schedules of the Controlled Substances Act.

Samidorphan, a chemical entity that is structurally similar to naltrexone, was a schedule II controlled substance, as it can be derived from opium alkaloids.

One psychiatrist and clinical investigator in favor stated that, “…samidorphan counters weight gain associated with clinical use of olanzapine as antipsychotic medication and this combination product offers significant advancement relative to olanzapine alone…”

Review of scientific and medical evaluations of samidorphan, as well as the recommendation to decontrol samidorphan from the US Department of Health and Human Services, bolstered this decision.

This action effectively removes regulatory controls and any administrative, civil, or criminal sanctions for controlled substances on samidorphan.

1. Drug Enforcement Administration. Schedules of controlled substances: removal of samidorphan from control. 

https://www.federalregister.gov/documents/2021/04/19/2021-07884/schedules-of-controlled-substances-removal-of-samidorphan-from-control

The Drug Enforcement Administration has freed this formerly schedule II controlled substance. 

Samidorphan: Scheduled Substance No More

Binge drinking is defined as consumption of 5 or more standard drinks on 1 occasion for males, or 4 or more for females, bringing blood alcohol concentration to 0.08 grams of alcohol per deciliter or higher.

 These drinking patterns lead to serious health and safety risks, including 

 from unintentional injuries such as motor vehicle crashes,

 suicide attempts as well as other mental health issues, legal charges, and, over the long term, damage to the liver and other organs.

Perhaps not surprisingly, national surveys have found that half of full-time 

 aged 18 to 22 years consumed alcohol in the previous month, and one-third engaged in binge drinking.

 In addition to the previously noted negative impacts, academic performance is also compromised, with 1 in 4 students endorsing academic difficulties (ie, missing class or falling behind on assignments) due to alcohol consumption.

 to perform poorly on tests and projects compared with those who drink but do not binge (40% vs 7%) and are 5 times more likely to miss a class.

 Although not all individuals who drink develop an addiction, consumption and especially binge drinking patterns are often preludes to an addiction, with approximately 9% of college students meeting criteria for alcohol use disorder.

 Lack of screening may also underestimate the magnitude of the problem.

The first few weeks of freshman year are often a period of heavy drinking and alcohol-related consequences. Social pressures and expectations during new-found independence, widespread availability and access to alcohol, unstructured schedules with mounting academic pressure, and lack of parental interactions all play a role. Alongside these stressors, many students have preexisting personality traits that may account for the use and misuse of alcohol during college.

Neuroticism, 1 of the 5 higher order personality traits, is defined by high emotional instability, depressed mood, low frustration tolerance, and anxiety. It also has been found to positively predict alcohol consumption (social intake within recommended parameters)

 and alcohol use (intake beyond recommended parameters that can lead to addiction).

 Only 1 previous study of 200 college students evaluated the implications of personality types; that study found high neuroticism and low conscientiousness predicted more 

aimed to better understand the role of personality and neuroticism in college alcohol use/misuse among freshman, above and beyond the reported levels of stress. The starting hypothesis revolved around the notion that negative affect faces of neuroticism, and primarily 

, are more strongly associated with alcohol use and misuse than stress when accounting for other personality domains.

 conducted a cross-sectional outpatient study, which was approved by the Institutional Review Board. Survey data was collected from participants during the first 8 weeks of their first college semester. Participants included 211 female and 90 male matriculating college freshmen with an average age of 18.58 years (SD = 0.39) from 2 campuses of a private university in the southeastern United States, spanning both urban and rural areas. Students were recruited via fliers posted on campus and during frequent in-person undergraduate events.

Data was acquired via online surveys of behavioral, health questionnaires, and cognitive assessments. Most surveys were completed within 3 weeks of the study initiation, and participants received a $15 gift card for completion. The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) and the Alcohol Use Disorders Identification Test (AUDIT) were used to assess alcohol use and misuse (

Endorsement of use 1 or more times on the ASSIST prompted the administration of the AUDIT, a 10-item questionnaire with a maximum score of 40 for which the higher scores indicate more severe and hazardous, harmful, excessive alcohol use/misuse. Stress was assessed using the Perceived Stress Scale (PSS), a 14-item self-reported measure of stress with each stress symptom scored on a 4-point Likert scale, where 0 = never and 4 = very often (maximum score of 56). Personality was assessed using the 44-item version of the Big Five Inventory (BFI), which measures 5 dimensions of personality (openness to experience, conscientiousness, extraversion, agreeableness, and neuroticism).

Ten facet traits were also calculated to assess more specific personality characterization within the 5 domains: openness, aesthetics, and ideas; conscientiousness, order, and self-discipline; extraversion, assertiveness, and activity; agreeableness, altruism, and compliance; and neuroticism, anxiety, and depression.

Analyses controlled for campus site (rural vs urban), sex, and individual week of study enrollment (school obligations as potential stressors fluctuated between study weeks). The investigators examined partial correlations between predictions while controlling for covariates. They used multiple regression analysis to examine the conditional and joint effect of personality and stress on alcohol use and misuse.

Of the sample, 54% (or 164 individuals) endorsed use of 

 at least once in their lifetime. Descriptive statistics of all covariates were accounted for, and across covariates sex and week of study enrollment were only modestly associated with AUDIT scores (male gender and more weeks since college commencement somewhat associated with higher AUDIT scores); site of the campus was not. Despite this, a t-test concluded that there were no gender differences between alcohol use and misuse (t(161) = -1.89, P = .06). Among partial correlations, the participants’ AUDIT scores were positively correlated with PSS scores (r = .17, P = .003) and neuroticism (r =.31, P < .001), and negatively correlated with agreeableness (r = −.12, P = .031). Stress was significantly correlated with all the personality domain scores except for openness to experience.

Regression analyses provided less biased estimates of personality and stress on AUDIT. To elucidate the relationship between neuroticism, stress, and 

 and misuse (given the discrepancy between the partial correlation results and the multiple regression model), the neuroticism facets were explored as outcome measures. Analyses that used the neuroticism facets (depression or anxiety) in place of the neuroticism domain found that neuroticism-depression was positively associated with higher AUDIT scores when accounting for PSS and domain-level 5 personality traits (β = .23, P = .028; adjusted R

Exclusion of all personality traits except for neuroticism-depression did not explain more variance in AUDIT (adjusted R

= .10, F (5, 152) = 4.56, P < .001). Interaction effects found that neuroticism as a domain moderated the relationship between PSS and AUDIT (β = .16, P = .040; adjusted R

 = .12, F (10, 146) = 3.16, P = 0.001). This interaction was found to be unique. Neuroticism-depression score moderated the relationship between PSS and AUDIT-T (β = .18, P = .020; adjusted R

 = .14, F(11, 145) = 3.22, P < .001. At low levels of the depression facet, stress was negatively associated with alcohol use and misuse, but at high levels of the depression facet, stress was positively associated with alcohol use and misuse (

This study supports the notion that neuroticism, and specifically the neuroticism-depression facet, appear to be the most robust predictors of alcohol use and misuse among incoming freshmen and could serve as useful population risk indicators. At low levels of the depression facet, stress was negatively associated with 

 and misuse; at high levels of the depression facet, however, stress was positively associated with alcohol use and misuse.

Investigators branched off previous studies exploring the roles of personality or stress on college drinking. They analyzed survey results data from Wave I of the MAPme Project, a longitudinal study of biobehavioral health and substance use during college. Those findings showed that personality characteristics and 

 play a significant role in the severity of problematic alcohol use and misuse, but certain traits are more significantly associated with alcohol involvement than others. The neuroticism-depression facet was a better predictor of alcohol use and misuse than the neuroticism domain, and this facet accounted for unique variance even when controlling for stress and other personality facets and domains. Stress did not account for unique variance in harmful and hazardous alcohol use and misuse beyond personality traits.

Unfortunately, this study had a number of limitations. Due to issues with the sample population, the findings may not generalize to other student populations. This study was conducted using a primarily Caucasian group from a private university located in the southeast US, without ensuring varied socioeconomic statuses. Similarly, although the sample encompassed both urban and rural participants, they were located in the same part of the country. The study also included a greater proportion of women compared to men, which may have skewed the baseline starting characteristics and outcomes.

Other issues can impact the findings. For instance, there were fairly low numbers of reported alcohol use among the sample to confidently generalize findings. Compensation offered to participants may add external biases and contribute to participant selection and participation.

The authors used a single-domain, self-reported assessment of stress, associated with increased likelihood of response bias and social desirability bias. More comprehensive and objective measures of stress levels might include physiological assessment, such as skin conductivity, heart rate, or cortisol measures that have shown be strongly associated with perceived stress.

The study employed the AUDIT-Total score, which confounds alcohol consumption and problematic alcohol use behaviors. The study participants reported low alcohol use and misuse behaviors, but the tool was not well prepared to detect unique effects of each of these constructs. Thus, future research could expand on this study by examining alcohol consumption and problems separately.

This study is limited by its cross-sectional design. To best examine the relationship between stress and personality on alcohol use and misuse, future studies could take a longitudinal state-trait perspective, treating personality and neuroticism specifically as stable traits and stress as a state.

Fortunately, data from this sample will continue to be collected until the students graduate, allowing longitudinal examinations into alcohol use and misuse trajectories, and the associations between stress, personality traits, and hazardous and harmful alcohol use.

So what does this mean for clinical practice? When presented with highly stressful circumstances, high neuroticism-depression in individuals predicts propensity to use and misuse alcohol. Similarly, people with high neuroticism-depression are likely to drink more when stressed, but low neuroticism-depression seems to be protective, with these individuals using and misusing alcohol at lower rates. Finally, the BFI domains and faces seem to have a role in alcohol use/misuse, above stress levels. These could be used as screeners for population risk indicators among incoming freshmen.

is assistant professor of psychiatry at Dartmouth’s Geisel School of Medicine and Director of Addiction Services at New Hampshire Hospital, Concord, NH. He is Addiction Section Editor for

The author reports no conflicts of interest concerning the subject of this article.

An earlier version of this article appeared online on February 10, 2021, under the title Neuroticism-Depression: What Is It and Does It Play a Role in College Drinking? and has since been updated for print. -Ed

1. National Institute on Alcohol Abuse and Alcoholism. NIAAA council approves definition of binge drinking. 

https://pubs.niaaa.nih.gov/publications/Newsletter/winter2004/Newsletter_Number3.pdf

2. Hingson R, Zha W, Smyth D. Magnitude and trends in heavy episodic drinking, alcohol-impaired driving, and alcohol-related mortality and overdose hospitalizations among emerging adults of college ages 18-24 in the United States, 1998-2014. 

3. Hingson R, Heeren T, Winter M, Wechsler H. Magnitude of alcohol-related mortality and morbidity among U.S. college students ages 18-24: changes from 1998 to 2001. 

4. US Department of Health and Human Services. Center for Behavioral Statistics and Quality, Substance Abuse and Mental Health Services Administration. 2019 National Survey on Drug Use and Health. Table 6.21B—Types of Illicit Drug, Tobacco Product, and Alcohol Use in Past Month among Persons Aged 18 to 22, by College Enrollment Status and Gender: Percentages, 2018 and 2019. Accessed February 5, 2021. 

https://www.samhsa.gov/data/sites/default/files/reports/rpt29394/NSDUHDetailedTabs2019/NSDUHDetTabsSect6pe2019.htm#tab6-21b

5. Wechsler H, Lee JE, Kuo M, et al. Trends in college binge drinking during a period of increased prevention efforts. Findings from 4 Harvard School of Public Health college alcohol study surveys: 1993-2001. 

The introduction of the heavy and frequent drinker: a proposed classification to increase accuracy of alcohol assessments in postsecondary educational settings

7. US Department of Health and Human Services. Center for Behavioral Statistics and Quality, Substance Abuse and Mental Health Services Administration. 2019 National Survey on Drug Use and Health. Table 6.23B—Alcohol Use Disorder in Past Year among Persons Aged 18 to 22, by College Enrollment Status and Demographic Characteristics: Percentages, 2018 and 2019. Accessed February 5, 2021. 

https://www.samhsa.gov/data/sites/default/files/reports/rpt29394/NSDUHDetailedTabs2019/NSDUHDetTabsSect6pe2019.htm#tab6-23b

8. Stanciu CN, Penders TM, Wuensch KL, et al. Underutilization of screening tools for alcohol use disorders – part I: results from survey of practices among North Carolina mental health providers and brief review of available instruments. J Alcohol Drug Depend. 2017;5(5):100282. Accessed February 5, 2021. 

https://www.longdom.org/open-access/underutilization-of-screening-tools-for-alcohol-use-disorderspart-iresults-from-survey-of-practices-among-north-carolina-mental-he-2329-6488-1000282.pdf

9. Allen MS, Vella SA, Laborde S. Health-related behaviour and personality trait development in adulthood. J Res Pers. 2015;59:104–110.

10. Cooper ML, Agocha VB, Sheldon MS. A motivational perspective on risky behaviors: the role of personality and affect regulatory processes. J Pers. 2000;68(6):1059-1088.

11. Loukas A, Krull JL, Chassin L, Carle AC. The relation of personality to alcohol abuse/dependence in a high-risk sample. J Pers. 2000;68(6):1153-1175.

12. Goldstein AL, Flett GL. Personality, alcohol use, and drinking motives: a comparison of independent and combined internal drinking motives groups. Behav Modif. 2009;33(2):182-198.

13. Ruiz MA, Pincus AL, Dickinson KA. NEO PI-R predictors of alcohol use and alcohol-related problems. J Pers Assess. 2003;81(3):226-236.

14. Martin KP, Benca-Bachman CE, Palmer RHC. Risk for alcohol use/misuse among entering college students: The role of personality and stress. Addict Behav Rep. 2020;13:100330. ❒

Although college drinking develops into an addiction, overconsumption and especially binge drinking patterns are often preludes to alcohol use disorder, with approximately 1 in 10 students meeting criteria for AUD.

Exploring the Link Between Neuroticism-Depression and College Drinking

Adial Pharmaceuticals, Inc. is filing an application for Fast Track with the US Food and Drug Administration (FDA) for its lead drug candidate, AD04.

Adial previously requested AD04, a therapeutic agent for the treatment of alcohol use disorder (AUD) in patients with target genotypes, be considered for the FDA expedited review program.

“We are working with our regulatory counsel to prepare our Fast Track submission after consultation with the FDA,” Adial’s CEO, William Stilley, said to the press “Following our submission, the FDA is expected to review the request and make a decision within 60 days.”

When a Fast Track application is reviewed, the submitted drug must demonstrate advantages over the currently available and approved therapy, thus meeting an unmet medical need. Advantages Adial believes AD04’s advantages include the following: 1) AD04 had a significant effect in patients with AUD who did not tolerate available therapy or failed to respond to said therapy; 2) AD04 saw a decrease in clinically significant toxicity of a common available therapy that often causes discontinuation of treatment; 3) AD04 has a safety and efficacy profile similar to that of available therapies, but is expected to enhance improvement in serious cases of AUD; 4) AD04 addresses the anticipated public health need.

“Adial’s correspondence and consultation with the FDA following its expedited review filing in September 2020, leads us to believe that AD04 qualifies for Fast Track consideration,” Adial’s Head of Regulatory, Jack Reich, PhD, commented to press. “I am confident Alcohol Use Disorder qualifies as a serious condition and that there is an unmet medical need, based on our communication with the FDA and as set forth in the FDA’s 

Guidance for Industry Expedited Programs for Serious Conditions—Drugs and Biologics

Cornel N. Stanciu, MD, MRO, had this to say: "You can look at the issue of pharmacotherapy for alcohol use disorders in two ways. On one hand, currently only 6% of those with an alcohol use disorder receive any of the FDA approved medications for relapse prevention, so we are not making use of what is available. On the other hand, addictionologists like myself need more tools to be able to tailor and personalize treatments for individual sufferers as one size does not fit all. This development presents a step forward towards a novel type of drug development to address an unmet medical need."

1. Adial Pharmaceuticals. Adial to file Fast Track application for AD04 with the FDA. News release. February 23, 2021. 

https://ir.adialpharma.com/press-releases/detail/112/adial-to-file-fast-track-application-for-ad04-with-the-fda

An alcohol use disorder treatment has 4 potential advantages over existing treatments.  

Hitting the Fast Track: Alcohol Use Disorder Treatment Filing with FDA

 of alcohol use disorders (AUD) with depression, one medication stood out as the most effective but is not widely used. The meta-analysis, which included 66 randomized controlled trials that tested 18 categories of medications in 5890 patients who had an AUD and either 

 or depressive symptoms, found that disulfiram was the most effective at reducing alcohol use across all comparisons.

Only 3 medications reached statistical significance for remission: disulfiram, anticonvulsants (carbamazepine, topiramate, tiagabine), and a naltrexone with a selective serotonin reuptake inhibitor (

). The odds ratio for remission was much higher with disulfiram, although the spread of the data was also wider as indicated by the standard deviations in the graph. This difference held up to sensitivity analysis, in which studies that might have skewed the results were removed.

For abstinence, only disulfiram and baclofen reached statistical significance. (Baclofen is a muscle relaxant with mixed results in AUD when studied independent of 

. It has no measurable reinforcing properties; there have been rare reports of baclofen abuse.) The odds ratio for days abstinent was higher for disulfiram compared with baclofen; this finding held up to sensitivity analysis (

, there were no clear winners. The noradrenergic medications appeared effective as a group, but this group included only venlafaxine and the non-US medication viloxazine. Nearly all efficacy was attributable to viloxazine, a norepinephrine reuptake inhibitor. Mirtazapine showed promise, but only in a secondary analysis of studies looking at full episodes of depression, rather than subsyndromal cases.

Although these studies cannot explain why disulfiram works well in depression, I will venture a guess from clinical experience. Patients with depression are often unable to take action on the things that are good for them, ie, bathing, eating healthy, and achieving sobriety. Although they want to stop drinking, they struggle with ruminative thoughts and never arrive at an executable plan. Disulfiram halts indecision, relieving them of the struggle. Patients are unlikely to drink on disulfiram because their actions are driven more by 

Disulfiram’s efficacy may not be unique to depression. The drug worked well in general AUD in prior analyses. In the 1930s, workers who were exposed to it at a rubber factory became sick after drinking alcohol. This led to the first clinical use in the 1940s and its FDA approval for alcohol cessation in 1951. However, only 200,000 individuals— about 1% of patients with AUD — take disulfiram in the US.

The reason for disulfiram’s decline may be due to its unique mechanism. Disulfiram induces an immediate hangover reaction when combined with alcohol. It blocks the enzyme that metabolizes acetaldehyde, the toxin responsible for alcohol’s hangover effect. With heavy drinking or high doses of disulfiram, this effect can be fatal. When disulfiram was first released, that effect was thought to be necessary, so patients were advised to drink. That practice ended when a few patients died, but it also left a stain on disulfiram’s reputation.

Oncologists do not withhold lifesaving medications because they are potentially toxic. Yet disulfiram appears underutilized, despite the fact that alcohol-related fatalities have soared to the No. 1 cause of death in middle-aged adults. Although fatalities are extremely rare with disulfiram, physicians may feel a greater weight of responsibility for those deaths than they do when patients die from 

. An oncologist, however, would not feel this way when a patient dies from 

 of disulfiram’s safety noted, “Deaths from the disulfiram-alcohol (ethanol) interaction have not been reported in recent years, possibly because the dosages used are lower than those used 40 years ago and patients with cardiac disease are now excluded from treatment.”

Today, most physicians prefer the lower dose of 250 mg/day. This produces a less toxic interaction with alcohol and works just as well as 500 mg/day. Actually, placebo worked just as well as disulfiram in the blinded studies because simply warning a patient that the interaction is toxic will help them achieve sobriety even when the pill is a placebo.

Patients must be alcohol free for 12 hours before starting disulfiram; the disulfiram-alcohol interaction persists for up to 2 weeks after stopping disulfiram. Disulfiram is contraindicated in severe 

 or heart failure, as there have been cases of sudden death after drug initiation. Relative contraindications include liver disease (disulfiram can elevate liver function tests, as can naltrexone), psychotic disorder (there are rare cases of psychosis or confusional states), and active alcohol use (in the past 12 hours). When used in absence of alcohol, common adverse effects include fatigue and headache. Check for drug interactions in the 

The bottom line seems pretty straightforward: Don’t overlook disulfiram, but know how to use it safely in 

is an instructor in clinical psychiatry at the Wake Forest School of Medicine and the director of the Mood Treatment Center in Winston-Salem, North Carolina. He is editor in chief of The Carlat Psychiatry Report and coeditor of the bipolar disorder section for

Efficacy of pharmacotherapeutics for patients comorbid with alcohol use disorders and depressive symptoms-a bayesian network meta-analysis

Safety issues concerning the use of disulfiram in treating alcohol dependence

Despite alcohol-related fatalities soaring to the No. 1 cause of death in middle-aged adults, this medication is often overlooked.

Underused Medication May Be Best Bet for Comorbid AUD and Depression

, half of full time college students aged 18 to 22 consumed alcohol this past month, and 33% of them engaged in binge drinking during this same time frame.

 as consumption of 5 or more standard drinks on 1 occasion for males, or 4 or more for females, bringing blood alcohol concentration to 0.08 grams of alcohol per deciliter or higher.

 These drinking patterns lead to serious health and safety risks, including death from unintentional injuries such as motor vehicle crashes,

 suicide attempts and other mental health issues, legal charges, and, over the long term, damage to the liver and other organs.

Academic performance is also compromised, with 1 in 4 students endorsing academic difficulties (ie, missing class or falling behind on assignments) due to alcohol consumption.

 to perform poorly on tests or projects compared to those who drink but do not binge (40% vs 7%) and 5 times more likely to have missed a class.

 Additionally, although not all who drink develop an addiction, consumption and especially binge drinking patterns are certainly preludes to developing an addiction, with approximately 9% of college students meeting criteria for alcohol use disorder.

Although most students arrive to college having already had some experience with alcohol, the first few weeks of freshman year are often a period of 

 and alcohol-related consequences. Social pressures and expectations during new-found independence, widespread availability and access to alcohol, an unstructured schedule with mounting 

, and lack of parental interactions all play a role. Alongside these stressors, many students have pre-existing personality traits that may account for the use and misuse of alcohol during college.

One of the “Big Five” higher order personality traits, neuroticism, defined by high emotional instability, depressed mood, low frustration tolerance, and anxiety, has been found to positively predict alcohol consumption,

 as well as being a predictor of alcohol use.

 As it pertains to the college population, only 1 previous study of 200 students evaluated the implications of personality types and found high neuroticism and low conscientiousness predicted more alcohol use and related problems.

In the study analyzed in this journal club, 

 aim to better understand the role of personality and neuroticism in college alcohol use/misuse among freshman, above and beyond the reported levels of stress. The starting hypothesis revolves around the notion that negative affect faces of neuroticism, and primarily depression, are more strongly associated with alcohol use and misuse than stress when accounting for other personality domains.

Do personality traits and neuroticism in particular predict 

 in matriculating college freshmen above and beyond reported levels of stress?

 Cross-sectional outpatient Institutional Review Board, an approved study with survey data collected from participants during the first 8 weeks of their first college semester.

211 female and 90 male matriculating college freshmen with an average age of 18.58 years (SD =0.39) from 2 campuses of a private university in the Southeastern United States, spanning both urban and rural areas.

Participants were recruited from the 2 campuses of a private university (urban n=193; rural n =110) at the start of the first semester through fliers posted around campus and during frequent in-person undergraduate events. They were administered an online survey of behavioral and health questionnaires, in addition to several 

. Most surveys were completed within 3 weeks of the study start, and participants received a $15 gift card for completion. The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) and the Alcohol Use Disorders Identification Test (AUDIT) were used to assess alcohol use and misuse (

Endorsement of use 1 or more times on the ASSIST prompted the administration of the AUDIT, a 10-item questionnaire with a maximum score of 40, where the higher scores indicate more severe and hazardous, harmful, 

. Stress was assessed using the Perceived Stress Scale (PSS), a 14-item self-reported measure of stress with each stress symptom scored on a 4-point Likert scale, where 0 =never and 4=very often (maximum score of 56). Personality was assessed using the 44-item version of the Big Five Inventory (BFI), which measures 5 dimensions of personality (openness to experience, conscientiousness, extraversion, agreeableness, and neuroticism).

Ten facet traits were also calculated to assess more specific 

 within the 5 domains: for openness, aesthetics, and ideas; conscientiousness, order, and self-discipline; for extraversion, assertiveness, and activity; agreeableness, altruism, and compliance; and for neuroticism, anxiety, and depression.

 All analyses controlled for campus site (rural versus urban), sex, and individual week of study enrollment (as school obligations as potential stressors fluctuated between study weeks). The researchers examined partial correlations between predictions while controlling for covariates. They used multiple regression analysis to examine the conditional and joint effect of personality and stress on alcohol use and misuse.

Of the sample, 54% (or 164 individuals) endorsed 

 at least once in their lifetime. Descriptive statistics of all covariates were accounted for, and across covariates sex and week of study enrollment were only modestly associated with AUDIT scores (male gender and more weeks since college commencement somewhat associated with higher AUDIT scores), while site of the campus was not. Despite this, a t-test concluded that there were no gender differences between alcohol use and misuse (t(161) =-1.89, 

=.06). Among partial correlations, the participants’ AUDIT scoreswere positively correlated with PSS scores (

< .001), and negatively correlated with agreeableness (

 was significantly correlated with all the personality domain scores except for openness to experience.

Regression analyses provided less biased estimates of personality and stress on AUDIT. To elucidate the relationship between neuroticism, stress, and alcohol use and misuse (given the discrepancy between the partial correlation results and the multiple regression model), the neuroticism facets were explored as outcome measures. Analyses that used the neuroticism facets(depression or anxiety) in place of the 

domain found that neuroticism-depression was positively associated with higher AUDIT scores when accounting for PSS and domain-level Big Five personality traits (

Exclusion of all personality traits except for neuroticism-depression did not explain more variance in AUDIT (Adjusted 

 < .001). Interaction effects found that neuroticism as a domain moderated the relationship between PSS and AUDIT (

=0.001). This interaction was found to be unique. Neuroticism-depression score moderated the relationship between PSS and AUDIT-T (

< .001. At low levels of the depression facet, stress was negatively associated with alcohol use and misuse, but at high levels of the depression facet, stress was positively associated with alcohol use and misuse (

 supports the notion that neuroticism, and the neuroticism-depression facet specifically, appear to be the most robust predictors of alcohol use and misuse among incoming 

 and could serve as useful population risk indicators for campuses. At low levels of the depression facet, stress was negatively associated with alcohol use and misuse, but at high levels of the depression facet, stress was positively associated with alcohol use and misuse.

This study tested an interesting hypothesis: do personality traits—and neuroticism in particular—predict alcohol use and misuse in matriculating freshmen above and beyond reported levels of stress?

Investigators branched off previous studies exploring the roles of personality or stress on college drinking. They analyzed survey results data from Wave I of the MAPme Project, a longitudinal study of biobehavioral health and substance use during college. The findings showed that personality characteristics and stress play a significant role in the severity of problematic alcohol use and misuse, but that certain traits are more significantly associated with alcohol involvement than others. The neuroticism-depression facet was a better predictor of alcohol use and misuse than the neuroticism domain, and this facet accounted for unique variance even when controlling for stress and other personality facets and domains. Stress did not account for unique variance in harmful and hazardous alcohol use and misuse beyond personality traits.

1. When presented with highly stressful circumstances, individuals’ high neuroticism-depression predicts propensity to use and misuse alcohol.

2. People with high neuroticism-depression are likely to drink more when stressed, but for individuals with low neuroticism-depression, the trait seems to be protective with these individuals using and misusing alcohol at lower rates.

3. The BFI domains and faces seem to have a role in alcohol use/misuse, above stress levels. These could be used as screeners for population risk indicators among incoming freshmen.

1. This study was conducted using a primarily Caucasian group from a private university located in the Southeast US. Findings may not generalize to other diverse individuals with varied socioeconomic statuses. Although it encompassed both urban and rural participants, they were located in the same part of the country.

2. Overall, looking at the big picture, there was a fairly low numbers of reported 

 among the sample to confidently generalize findings.

3. The study included a greater proportion of women compared to men, which may have skewed the baseline starting characteristics and outcomes.

4. Compensation offered to participants may add external biases and contribute to participant selection and participation.

5. The authors used a single-domain,hear self-reported assessment of stress, associated with increased likelihood of response bias and social desirability bias. More comprehensive and objective measures of stress levels might include physiological assessment, such as 

, or cortisol measures that have shown be strongly associated with perceived stress.

6. Here the authors used the AUDIT-Total score, which confounds 

 and problematic alcohol use behaviors. As they note, while the study participants reported low alcohol use and misuse behaviors and were not well prepared to detect unique effects of these constructs, future research could expand on the present study by examining alcohol consumption and problems separately.

 is limited by its cross-sectional design. To best examine the relationship between stress and personality on alcohol use and misuse, future studies could take a longitudinal state-trait perspective, treating personality and neuroticism specifically as stable traits and stress as a state. Data from this sample will continue to be collected until the students graduate, allowing longitudinal examinations into alcohol use and misuse trajectories, and the associations between stress, personality traits, and hazardous and harmful alcohol use.

TM. The author reports no conflicts of interest concerning the subject matter of this article.

1. US Department of Health and Human Services. Center for Behavioral Statistics and Quality, Substance Abuse and Mental Health Services Administration. 2019 National Survey on Drug Use and Health. Table 6.21B—Types of Illicit Drug, Tobacco Product, and Alcohol Use in Past Month among Persons Aged 18 to 22, by College Enrollment Status and Gender: Percentages, 2018 and 2019. Accessed February 5, 2021. 

2. National Institute on Alcohol Abuse and Alcoholism. NIAAA council approves definition of binge drinking. 

3. Hingson R, Zha W, Smyth D. Magnitude and trends in heavy episodic drinking, alcohol-impaired driving, and alcohol-related mortality and overdose hospitalizations among emerging adults of college ages 18-24 in the United States, 1998-2014. 

4. Hingson R, Heeren T, Winter M, Wechsler H. 

Magnitude of alcohol-related mortality and morbidity among U.S. college students ages 18-24: changes from 1998 to 2001

8. Stanciu CN, Penders TM, Wuensch KL, et al. Underutilization of screening tools for alcohol use disorders – part I: results from survey of practices among North Carolina mental health providers and brief review of available instruments. 

. 2017;5(5):100282.Accessed February 5, 2021. 

9. Allen MS, Vella SA, Laborde S. Health-related behaviour and personality trait development in adulthood. 

10. Cooper ML, Agocha VB, Sheldon MS. A motivational perspective on risky behaviors: the role of personality and affect regulatory processes. 

11. Loukas A, Krull JL, Chassin L, Carle AC. The relation of personality to alcohol abuse/dependence in a high-risk sample. 

12. Goldstein AL, Flett GL. Personality, alcohol use, and drinking motives: a comparison of independent and combined internal drinking motives groups. 

13. Ruiz MA, Pincus AL, Dickinson KA. NEO PI-R predictors of alcohol use and alcohol-related problems. 

14. Martin KP, Benca-Bachman CE, Palmer RHC. 

Risk for alcohol use/misuse among entering college students: The role of personality and stress

Are people with high "neuroticism-depression" likely to drink more than the average person when stressed? We may be getting closer to the answer. 

Neuroticism-Depression: What Is It and Does It Play a Role in College Drinking?

There is evidence for an increased prevalence of comorbid substance use disorders (SUDs) in patients with bipolar disorder (BD), even when 

 found that the lifetime prevalence of alcohol abuse or dependence in bipolar I and II disorder was 46% and 39%, respectively. A more 

 of 43,000 respondents found a 24% 12-month and 56% lifetime prevalence of any alcohol use disorders (AUD) in patients with bipolar I disorder.

 that comorbid AUD is associated with a more complicated illness course and poorer outcomes in patients with BD.

Most studies of comorbid BD and AUD have been retrospective, and few prospective studies have differentiated between bipolar I and II disorders. Using the COGA sample (Collaborative Study on Genetics in Alcoholism), 

 directly compared patients who had bipolar I and II disorders with and without comorbid alcohol dependence. These patients were assessed at baseline and then prospectively reinterviewed after 5 years.

COGA enrolls treatment-seeking probands with 

 (and their relatives) at 6 centers in the United States. Exclusion criteria are life-threatening medical disorders, repeated intravenous drug use, and an inability to speak English. Patients were interviewed at baseline, as well as after approximately 5 years using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA). The SSAGA contains an assessment of 17 DSM-IV diagnoses, including BD, as well as the timing of symptom onset and remission.

Altogether, 228 participants with bipolar I disorder or bipolar II disorder were identified. One-hundred seventy-two patients had a comorbid diagnosis of alcohol dependence (N = 56 with bipolar II [Group 2] and 116 with bipolar I [Group 4]). Fifty-six individuals did not have 

Are there differences in the clinical course of bipolar I and bipolar II disorder with and without comorbid alcohol use disorder?

Alcohol Abuse

Patent Brings Psychiatry One Step Closer to Precision Medicine

Samidorphan: Scheduled Substance No More

Exploring the Link Between Neuroticism-Depression and College Drinking

Hitting the Fast Track: Alcohol Use Disorder Treatment Filing with FDA

Underused Medication May Be Best Bet for Comorbid AUD and Depression

Neuroticism-Depression: What Is It and Does It Play a Role in College Drinking?

Don't Raise a Glass: Alcohol Dependence Complicates Bipolar Disorder

Alcohol Abuse and Stroke

Schizophrenia and AUD

Less Risky Than Believed: Alcohol and Cannabis Combinations