Alcohol and drug use disorders among adults with ADHD: Prevalence and associations with ADHD symptom severity and emotional dysregulation.

Background High risk of substance use disorders (SUD) in people with ADHD calls for exploratory research. The aim of this study was to estimate the prevalence of alcohol use disorder (AUD) and drug use disorder (DUD) in a clinical sample of adults with ADHD, and to examine their association with ADHD symptom severity and emotional dysregulation (ED). Methods The study sample consisted of patients who were admitted to a private psychiatric outpatient clinic in Oslo between 2014 and 2018. Out of 612 patients diagnosed with ADHD, 585 (96.5%) agreed to participate in the study. ADHD was diagnosed according to DSM-5 criteria. AUD and DUD were diagnosed using the Mini International Neuropsychiatric Interview (M.I.N.I.). ADHD severity was assessed by the Adult ADHD Self Report Scale (ASRS). Emotional Dysregulation (ED) was assessed by the eight-item version of Barkley’s Current Behavior Scale - Self Report (CBS-SR). Results The 12-month prevalence of AUD and DUD was 5.3% and 13.7%, respectively. The lifetime prevalence was 12.0% for AUD and 27.7% for DUD. A history of DUD, but not AUD, was positively associated with hyperactivity-impulsivity ADHD core symptoms, as well as ED. Conclusions The prevalence of lifetime DUD among patients with ADHD is high and associated with higher levels of hyperactivity-impulsivity symptoms, as well as ED. It is important to consider comorbid DUD in adult ADHD patients, particularly among individuals with high levels of hyperactivity-impulsivity ADHD core symptoms or ED.

multitude of additive and interactive genetic and environmental factors operating in a highly complex manner (2,3,4).
The prevalence of ADHD in the general adult population is estimated to be 3%-5% (5,6).
ADHD is a dimensional diagnosis where attention deficits and hyperactivity-impulsivity may appear in various degrees and combinations (7).
The co-occurrence of ADHD and substance use disorders (SUD) such as alcohol use disorder (AUD) or drug use disorder (DUD) has been studied in a variety of clinical and research settings. Overall, there is an earlier onset and elevated risk of SUD in people with ADHD (6,(8)(9)(10)(11)(12)(13)(14)(15)(16)(17), but the direction of causality, underlying mechanisms and clinical implications of the strong association between ADHD and SUD are still unclear.
It is well documented that many patients with ADHD are striving to regulate negative emotions (18)(19)(20), and may be quick to anger, easily frustrated and emotionally overexcitable, a symptom cluster defined as Emotional Dysregulation (ED) (21,22). Although ED may be understood as a transdiagnostic factor in the development of psychopathology (23) it appears to be specifically related to impulsivity (24). ED has been found to be associated with SUD in children and adolescents with ADHD (25).
The strong relationship between ADHD and ED (18)(19)(20) makes it challenging to determine whether it is ADHD severity per se or concurrent ED that is most strongly related to SUD.
The aim of the present study was to estimate the prevalence of AUD and DUD in a clinical sample of adults diagnosed with ADHD, and to examine their associations with ADHD symptom severity and ED.

Participants
The study sample consisted of adult patients, age range from 18 to 69, who fulfilled the criteria for ADHD. They were admitted to a psychiatric clinic in Oslo, Norway, which was specialized in psychiatric examinations and treatment of ADHD. Recruitment was conducted in the years between 2014 and 2018. During these years, a total of 612 patients were found fulfilling the diagnostic criteria of ADHD and were asked to participate in the study. Sixty five percent of patients assessed were self-referred, and 35 % were referred by general physicians, psychiatrists, neurologists or neuropsychologist.
Out of 612 patients with ADHD, 585 (95.6%) gave their written consent to participate and were included in the study. The study was approved by the Regional Medical Ethics ADHD symptom severity was measured using the Adult ADHD Self-Report Scale (ASRS) Symptom Check List, v1.1 by WHO 2007. The ASRS is a reliable and valid screening instrument for evaluating ADHD in adults (29). This 18-item version yields a score ranging from 0 to 72 points. We recorded subdivisions of the ASRS questionnaire, as inattentive items (item 1-4 and 7-11) and hyperactive/impulsivity items (item 5, 6, and [12][13][14][15][16][17][18] separately (30).
ED was assessed by a questionnaire with eight items from the 99 items Current Behavior Scale -Self Report (CBS-SR) questionnaire (31,32,33). This 8-item version yields a score ranging from 0 to 24 points (Table 1).

Statistical analysis:
We performed chi-square tests or t-tests to compare sociodemographic characteristics between women and men. We used logistic regression analyses to examine associations between alcohol and drug use disorders as dependent variables and ADHD symptom severity and ED as independent variables. All tests were two-tailed, and differences were considered significant if p<0.05. All statistical analyses were done using the software package IBM 2016 SPSS version 22. Table 2 shows sociodemographic and clinical characteristics of men (n=317) and women (n=268) in the study. More women than men were living with children and women reported higher levels of ADHD symptoms and ED compared to men. Table 3 shows the 12-month prevalence and lifetime prevalence of AUD and DUD in men and women. Both men and women had considerable higher prevalences of DUD than AUD, and men had higher prevalences of both AUD and DUD compared to women.

Results
In the total sample 27.7% (n=162) of the participants had a history of lifetime DUD.
Among these participants, the frequency of drug abuse was: amphetamine 69.1% (n=112), cannabis 61.7% (n=100), cocaine or ecstasy 26.5% (n=43), benzodiazepines 26.5% (n=43), heroin or other opioids 10.5% (n=17) and unspecified drugs 16.0% (n=26). Tables 4 and 5 show associations between lifetime SUD and clinical characteristics including hyperactivity-impulsivity and ED. Lifetime AUD was not significantly associated with the levels of ADHD symptoms or ED when adjusted for gender and age (Table 4). In contrast, lifetime DUD was significantly associated with both hyperactivity-impulsivity and ED (Table 5).

Discussion
In our clinical sample of adults with ADHD we observed a 12-month prevalence of 5.3% for AUD and 13.7% for DUD. The lifetime prevalence was 12.0% for AUD and 27.7% for DUD.
All prevalence rates were higher for men than for women.
The 12-month prevalence of AUD was similar to the general population prevalence in Norway and US (34,35,36). In contrast, the 12-month prevalence of DUD (13.7%) was considerably higher than the 3.9% prevalence in the US population (37). A similar pattern was found for lifetime prevalence of AUD and DUD. While the lifetime prevalence of AUD in our study was lower than that in the general Norwegian or US population, the lifetime prevalence of DUD was considerably higher (34,35,36,38).
Our findings demonstrate the need to distinguish between different types of SUD in the understanding of comorbidity in patients with ADHD. The findings that DUD, in contrast to AUD, was far more prevalent than in the general population, as well as our findings that DUD, but not AUD, was associated with increased ED and ADHD symptom severity, corresponds to several findings in the literature. First, genome wide association studies have shown strong genetic correlations between ADHD and DUD (39,40), while some genetic factors contributing to the risk of developing AUD are negatively correlated with ADHD (41). Second, there may be some shared environmental determinants for ADHD and DUD (40) for example maternal DUD (42). Third, it has been suggested that drug dependence, especially the misuse of amphetamine and cannabis, is the result of selfmedication related to ADHD symptoms (43,44,45). In our sample, amphetamine and cannabis were the preferred substances of misuse.
The higher prevalence rates of AUD and DUD in men compared to women are in accordance with gender differences in the general population (34,35,36,37). In line with others we find that women reported higher levels of hyperactivity-impulsivity (46) and ED (47) compared with men. This is still consistent with our findings that hyperactivityimpulsivity and ED in both women and men are associated with DUD.
Our observation that DUD was associated with ED is consistent with findings that ED in general increases the risk of developing and maintaining drug addiction (48). DUD typically appears later in life than ADHD and ED, suggesting that DUD is modified by ADHD and ED, rather than vice versa. Nevertheless, it is possible that DUD may reinforce the symptoms of both ADHD and ED.

Methodological considerations
Patients attended to a private, not governmental funding ADHD clinic may not be representative for patients with ADHD in general. They may have a higher socio-economic status, compared to public outpatient clinics or hospitals. Also, the prevalence of morbidity may not be representative for the total ADHD patient population. Still, the reported prevalence rates in our study were similar to recently reported prevalence rates for the total Norwegian population (17).
The cross-sectional design limits the interpretation of causal relationships.

Conclusions
In this study of adult ADHD patients, we found a high prevalence of DUD. DUD was independently associated with both higher symptom levels of hyperactivity-impulsivity and ED. Thus, a co-morbid DUD should be considered in adult ADHD patients, particularly among individuals with high levels of hyperactive-impulsive ADHD core symptoms or ED.

Clinical implications
The causal mechanisms of the relationship between ADHD and DUD are not known, but self-medication for hyperactivity-impulsivity and ED is a likely possibility. Thus, early recognition and targeted interventions may be necessary to prevent the negative consequences of ADHD.

Consent for publication: Not applicable
Availability of data and materials: Data are from a private psychiatric outward in Oslo.
Public availability would compromise privacy of the respondents. According to the approval from the Norwegian Regional committees for medical and health research ethics, the data is to be stored properly and in line with the Norwegian Law of privacy protection.
However, anonymized data is freely available to interested researchers upon request, pending ethical approval from the ethics committee. Interested researchers can contact project leader Espen Anker (espen.anker@online.no) with requests for the data.