Sex differences in comorbidity between substance use and mental health in adolescents: Two sides of the same coin

Sergio Fernández-Artamendi, Víctor Martínez-Loredo, and Carla López-Núñez 36 Despite the substantial functional impairment associated with the coexistence of SUD and MHD in adolescents (Roberts et al., 2007), and recent recommendations to integrate their care (Brewer et al., 2017), research on adolescent comorbidity is still scarce and inconclusive (Skogen et al., 2014). Among the substances used by adolescents, alcohol and cannabis present some of the highest prevalences (Plan Nacional Sobre Drogas, 2019), raising concern given the increased risk of further alcohol and cannabis use disorders (Duncan et al., 2015). It is estimated that 20% of adolescents may experience a mental health problem during their adolescence (World Health Organization, 2003). Data indicates that 7.4% of children between 3 and 17 have a behavioral disorder, 7.1% have a diagnosis of anxiety, and up to 3.2% have depression (Ghandour et al., 2018). In Spain, 3.2% of boys and 4.8% of girls between 15 and 24 years of age have a mental disorder. Particularly, 1.1% of boys and 1.4% of girls have a depressive disorder, and 1.1% of boys and 3.0% of girls have an anxiety disorder (Ministerio de Sanidad, Consumo y Bienestar Social, 2017). The association between adolescent drinking and externalizing problems has been widely reported (Bousoño Serrano et al., 2019; Colder et al., 2013; Colder et al., 2017; Strandheim et al., 2011; Pedersen et al., 2018). Different studies also indicate that a signifi cant association exists in adolescents between drinking (Gonzálvez et al., 2020), problem drinking (Chhoa et al., 2019), high-risk drinking (Ritcher et al., 2016) and depression; and between alcohol use (Ritcher et al., 2016), high-risk drinking (Villarosa et al., 2014), alcohol abuse (Low et al., 2008) and anxiety. Also, higher prevalence of alcohol use disorders (AUD) has been reported among adults with obsessive-compulsive disorder (Gentil et al., 2009). Although a clear and consistent association between internalizing symptoms and alcohol use problems is still not ISSN 0214 - 9915 CODEN PSOTEG Copyright © 2021 Psicothema www.psicothema.com Sex Differences in Comorbidity Between Substance Use and Mental Health in Adolescents: Two Sides of the Same Coin Sergio Fernández-Artamendi1, Víctor Martínez-Loredo2, and Carla López-Núñez1 1 Universidad Loyola Andalucía, and 2 Universidad de Zaragoza Abstract Resumen Background: This study aims to evaluate sex differences in alcohol and cannabis use and mental health disorders (MHD) in adolescents, and to evaluate the predictive role of mental health disorders for alcohol and cannabis use disorders (AUD and CUD respectively). Method: A sample of 863 adolescents from the general population (53.7% girls, Mage = 16.62, SD = 0.85) completed a computerized battery including questions on substance use frequency, the Brief Symptom Inventory, the Cannabis Problems Questionnaire for Adolescents – Short version, the Rutgers Alcohol Problem Index and the DSM-IV-TR criteria for AUD and CUD. Bivariate analyses and binary logistic regressions were performed. Results: Girls presented signifi cantly more mental health problems and a higher prevalence of comorbidity between SUD and MHD. Obsessivecompulsive symptoms and phobic anxiety indicated a higher risk of AUD, whereas depression and interaction between hostility and obsessivecompulsive disorder indicated a higher risk of CUD. Conclusions: Comorbidity between SUD and MHD is high among adolescents, and signifi cantly higher among girls. Keywords: Alcohol, cannabis, mental health, gender differences, adolescents. Diferencias de Sexo en Comorbilidad entre Consumo de Sustancias y Salud Mental en Adolescentes: Dos Caras de la Misma Moneda. Antecedentes: el objetivo de esta investigación es evaluar las diferencias de sexo en el uso de cannabis y alcohol y en trastornos de salud mental TSM en adolescentes, y el rol predictivo de los TSM sobre los trastornos por uso de alcohol y cannabis (TUA y TUC, respectivamente). Método: una muestra de 863 adolescentes de la población general (53,7% chicas, edad media = 16.62, DT = 0,85) completaron una batería informatizada sobre la frecuencia de uso de sustancias, el Inventario Breve de Síntomas, el Cuestionario de Problemas por Consumo de Cannabis - versión breve, el Índice de Rutgers de Problemas con el Alcohol y los criterios DSM-IVTR para el TUA y TUC. Se realizaron análisis bivariados y de regresión logística binaria. Resultados: las chicas presentaron signifi cativamente más problemas de salud mental y mayor prevalencia de comorbilidad entre TUS y TSM. El trastorno obsesivo-compulsivo (TOC) y la ansiedad fóbica indicaron un mayor riesgo de TUA, mientras que la depresión y la interacción entre hostilidad y TOC indicaron mayor riesgo de TUC. Conclusiones: la comorbilidad entre TUS y TSM es alta entre los adolescentes, y signifi cativamente mayor entre las chicas. Palabras clave: alcohol, cannabis, salud mental, diferencias de género, adolescentes. Psicothema 2021, Vol. 33, No. 1, 36-43 doi: 10.7334/psicothema2020.297 Received: August 10, 2020 • Accepted: October 10, 2020 Corresponding author: Sergio Fernández-Artamendi Departamento de Psicología Universidad Loyola Andalucía 41704 Dos Hermanas (Spain) e-mail: [email protected] Sex Differences in Comorbidity Between Substance Use and Mental Health in Adolescents: Two Sides of the Same Coin 37 evident (Homman et al., 2016), it has been associated with selfmedication purposes (Foster et al., 2018). This is not surprising since the risk of addiction in adolescents has been linked to poor emotional regulation (Cornellà-Font et al., 2020). Other studies have failed to detect signifi cant associations between alcohol and internalizing problems (Pedersen et al., 2018). Cannabis use has been consistently associated to externalizing problems (e.g., Griffi th-Lendering et al., 2011; Pedersen et al., 2018). It has been also repeatedly associated with internalizing problems in adolescents, such as depression (Rasic et al., 2013) and anxiety (Kedzior & Laeber, 2014). Other studies have failed to detect signifi cant associations between cannabis use and internalizing symptoms (Griffi th-Lendering et al., 2011), or cannabis abuse and anxiety (Low et al., 2008). Comorbidity between cannabis use and obsessive-compulsive disorders in young adults (Spradin et al., 2017) has also been reported. Finally, while abundant research has linked cannabis use in adolescents with an increased risk of psychosis later on (Marconi et al., 2016), this association in adolescents might disappear when accounting for confounding variables (Fonseca-Pedrero et al., 2020). Furthermore, research with adult populations has consistently shown that sex differences exist in the prevalence and features of the comorbidity between MHD and SUD (e.g., Frem et al., 2017; Khan et al., 2013). However, not many studies have evaluated sex differences in the association between mental health and substance use problems in adolescents, and inconsistent results have been reported. Data has shown that girls with SUD often present with higher rates of comorbidity (Robert et al., 2007), and girls in SUD treatment present with higher levels of mental health problems. Other studies failed to fi nd signifi cant sex differences in the associations between mental health symptoms and alcohol and other drugs use (Heradsveit et al., 2018). Evidence-based interventions taking into account both SUD and MHD in adolescents are currently underdeveloped (Brewer et al., 2017). In order to design tailored treatment strategies, clarifying this specifi c association between SUD and MHD seems crucial. Moreover, more research is needed to be able to identify specifi c treatment approaches that address sex differences in comorbidity, particularly among adolescents (Dir et al., 2017). The purpose of this study is two-fold: 1) to evaluate sex differences in alcohol and cannabis use patterns and mental health symptoms, and 2) to evaluate the predictive role of MHD with regards to alcohol and cannabis use disorders. With this aim, secondary analyses have been carried out with data from a research study conducted between 2010 and 2012 (Fernández-Artamendi et al., 2013). Method Participants The initial sample was made up of 863 adolescents from nine high schools offering academic and technical courses from the Principality of Asturias (Spain). The exclusion criteria for this study were: 1) Not providing a valid questionnaire according to the criteria established by the Infrequency Scale, as indicated below and 2) being 18 years of age or older. A total of 772 participants provided a valid questionnaire (89.5%) and 684 were 18 years or younger (79.26% of the initial sample). These 684 participants (53.7% girls; mean age = 16.62 years; SD = 0.852) made up the fi nal sample. The descriptive characteristics of participants are shown in Table 1. Instruments Sociodemographic information. Participants were requested to provide information on their age and sex. Frequency and patterns of alcohol and cannabis use in the last month were evaluated through the items of the European School Survey Project on Alcohol and Other Drugs Student Questionnaire (European Monitoring Centre for Drugs and Drug Addiction [EMCDDA], 2007). These questions measured the frequency of substance use using a Likert scale (1-7) corresponding to 7 alternatives (namely: never/1-2 times/3-5/6-9/10-19/20-39/more than 40 times). Alcohol-related problems. To detect the presence of alcoholrelated problems, the Spanish version (López-Núñez et al., 2012) of the Rutgers Alcohol Problem Index (RAPI; White & Labouvie, 1989), validated in this study, was used. Only those adolescents reporting any alcohol use were presented the RAPI. This version has shown excellent reliability (Cronbach’s α = .91) with adolescents (López-Núñez et al., 2012). The self-report includes 23 questions with Likert-type responses (where 0 = never; 1 = 1 to 2 times; 2 = 3 to 5 times; 3 = more than 5 times) on the frequency of alcoholrelated events that occurred in the previous year. A cut-off level of 7 points in the RAPI showed a high reliability (Cronbach’s Alpha = .87) and a sensitivity and specifi city of 81.9% and 71.3% respectively for alcohol dependence. Cannabis-related problems. To evaluate problems associated to cannabis use, the Spanish version (Fernández-Artamendi et al., 2012) of the Cannabis Problems Questionnaire for Adolescents – Short Form (CPQ-A-S; Proudfoot et al., 2010), validated as part of this study, was used. Only adolescents reporting any cannabis use were presented the CPQ-A-S. This questionnaire includes 12 dichotomous items on the presence of different problems commonly associated to cannabis use. Reliability of CPQ-A-S is moderate (Cronbach’s Alpha = .70). A score of 3 points presents a sensitivity and specifi city of 83% and 77.5% respectively for cannabis dependence (Fernández-Artamendi et al., 2012). Presence of a DSM-IV-TR diagnosis of abuse or dependence of alcohol and cannabis was evaluated by means of self-reported dichotomous questions on the corresponding criteria. According to DSM-IV-TR (American Psychological Association [APA], 2000) presence of one or more symptoms of abuse was considered a diagnosis of alcohol/cannabis abuse, and presence of three or more criteria of dependence, was considered a diagnosis of alcohol/ cannabis dependence (clustered within a year). For analytic purposes, diagnoses were merged into alcohol use disorder (AUD) in case alcohol abuse or alcohol dependence was detected; and cannabis use disorder (CUD) in case cannabis abuse or cannabis dependence was detected. Psychopathological problems were assessed by means of the Brief Symptom Inventory (BSI) by Derogatis and Melisaratos (1983). This instrument yields scores on nine dimensions and one global index: somatization, obsessive-compulsive (OCD), interpersonal sensitivity (IS), depression, anxiety, hostility, phobic anxiety, paranoid ideation, psychoticism, and Global Severity Index (GSI). Reliability of each dimension of the BSI ranges between .72 and .95 (Pereda et al., 2007). Following the administration manual of the BSI (Derogatis & Melisaratos, 1983), positive diagnoses for each dimension were calculated following normative scores. An infrequency scale was included in the assessment battery in order to detect questionnaires that had been fi lled up in a random Sergio Fernández-Artamendi, Víctor Martínez-Loredo, and Carla López-Núñez 38 or erratic manner. The instrument was the Oviedo Infrequency Scale (INF-OV; Fonseca-Pedrero et al., 2009) which evaluates the participants’ agreement or disagreement with 12 items such as the following: ‘Have you ever seen a fi lm on television?’. Following the rules established by the authors, questionnaires with more than three wrong answers were excluded from statistical analyses. Procedure All the data was collected through self-administered questionnaires that were included as part of a computerized survey that permits the design and application of an adaptive test with all the instruments. The software was set up to alert respondents if they gave an incongruent answer and to warn them if they left any blank item. All students in courses aimed at adolescents with ages ranging from 14 to 18 years (from the third year of secondary education up to technical training and baccalaureate courses), from nine randomly selected high schools in the region, participated in the study. The study was approved by the Ethics Committee of the Ministry of Science and Innovation, and the Department of Education of the regional government. Individual and family consent was obtained through the schools following their regular protocols. All participants fi lled up the questionnaires in their own classrooms, with no teaching staff present. Trained researchers supervised the application of the survey, guaranteeing that students respected the privacy of their classmates Data analysis First of all, descriptive analyses of demographic variables, substance use, substance use problems and mental health symptoms were calculated, for the full sample and by sex. Analysis of variance (ANOVA) and chi-square statistic with Yates correction for continuity were carried out to evaluate sex differences in continuous variables evaluating substance use, substance use problems and mental health symptoms. Secondly, chi-square statistics with Yates correction for continuity, and the Fisher exact test were carried out to evaluate sex differences in the prevalence of MHD, according to thresholds established by the BSI, among participants with AUD and CUD. Effect sizes were calculated using Phi coeffi cient (Φ) and eta-squared for all the aforementioned chi-square and ANOVA calculations, respectively. Confi dence level was set at 95%. Thirdly, two logistic regressions were carried out to evaluate the predictive role of a positive diagnosis in each mental health dimension with regards to the presence of AUD or CUD. With this purpose, fi rstly, chi square odd ratios for each mental health diagnosis and AUD/ CUD were calculated. Those variables reporting signifi cant odd ratios were included in the model. Secondly, possible interactions between mental health diagnoses and sex, and between every two mental health diagnoses were calculated with the Breslow-Day test. Signifi cant interactions were also included in the models. Finally, two independent logistic regression models (one for AUD, and one for CUD) were carried out with backwards stepwise elimination conditional model. Confi dence level was 95%. The statistical package SPSS Version 26.0 was used for all analyses. Results Descriptive results (Table 1) indicate that frequent (monthly) use of alcohol is considerably prevalent in this sample (77.5%), and that 29.8% of adolescents report having intoxicated with alcohol at least once in this period; with no signifi cant sex Table 1 Descriptive analyses and gender differences in substance use prevalence, substance use problems and mental health scores Total (n = 684) [M (SD)] Boys (n = 367) [M (SD)] Girls (n = 317) [M (SD)] Statistic (p-value) Effect size Age 16.62 (0.85) 16.76 (0.87) 16.45 (0.80) 23.60 (≤.001)1.033 Alcohol last month (%) 77.5% 79.0% 75.7% 0.886 (.346)2-.040 Drunk last month (%) 29.8% 32.7% 26.5% 2.834 (.092)2-.068 Cannabis last month (%) 17.7% 22.3% 12.3% 11.097 (.003)2-.131 RAPI (among drinkers) 6.12 (7.55) 6.66 (7.92) 5.49 (7.05) 4.121 (.043)1.006 CPQ-A-S (among users) .57 (1.45) .74 (1.69) .36 (1.08) 4.604 (.033)1.017 AUD (%) 27.2% 33.0% 20.5% 12.727 (≤.001)2-.140 CUD (%) Somatization OC IS Depression Anxiety Hostility Phobic Anxiety Paranoid ideation Psychoticism 9.6% 0.99 (0.85) 0.89 (0.86) 0.79 (0.84) 1.08 (0.75) 1.06 (0.84) 0.96 (0.92) 0.92 (0.86) 0.96 (0.89) 0.93 (0.82) 14.4% 0.92 (0.89) 0.82 (0.85) 0.77 (0.85) 1.02 (0.78) 1.04 (0.86) 0.91 (0.95) 0.89 (0.88) 0.83 (0.88) 0.90 (0.83) 4.1% 1.06 (0.79) 0.96 (0.86) 0.81 (0.83) 1.14 (0.71) 1.09 (0.82) 1.01 (0.87) 0.95 (0.84) 1.11 (0.88) 0.98 (0.81) 19.691 (≤.001)2 5.004.(026)1 4.590 (.033)1 .363 (.547)1 3.983 (.046)1 .724 (.395)1 1.970 (.161)1 .804 (.370)1 16.894 (≤.001)1 1.665 (.197)1 -.175 .007 .007 .001 .006 .001 .003 .001 .024 .002 GSI 0.42 (0.46) 0.38 (0.45) 0.46 (0.46) 4.877 (.028)1.007 Notes: RAPI: Rutgers Alcohol Problem Index; CPQ-A-S: the Cannabis Problems Questionnaire for Adolescents – Short Form; AUD: Alcohol Use Disorder; CUD: Cannabis Use Disorder; OCD: Obsessive-Compulsive Disorder; IS: Interpersonal Sensitivity; GSI: Global Severity Index 1ANOVA; 2Chi-square Sex Differences in Comorbidity Between Substance Use and Mental Health in Adolescents: Two Sides of the Same Coin 39 differences. However, among drinkers, boys presented with a signifi cantly higher severity of alcohol-related problems according to the RAPI. As of cannabis, signifi cantly more boys (22.3%) than girls (12.3%) had used it in the last month. Among cannabis users, boys presented also with signifi cantly more cannabis-related problems. The prevalence of AUD and CUD was also signifi cantly higher among boys. Regarding mental health, girls presented with signifi cantly more symptoms of somatization, paranoid ideation, OC and depression. Results of the GSI also show signifi cantly higher scores among girls. For all mental health dimensions, the effect sizes were small, except for paranoid ideation, which was between medium and large. As reported in Table 2, among adolescents with AUD, a signifi cantly higher number of girls resulted positive for somatization, paranoid ideation and hostility. Among adolescents with CUD, girls were more likely to be positive for OCD, hostility and interpersonal sensitivity. Also, girls with CUD presented with a higher prevalence of positive cases than boys according to the GSI. Finally, two logistic regression models were calculated. Regarding the AUD model, preliminary analyses indicated that anxiety, obsessive-compulsive, hostility, depression, phobic anxiety and the interaction between depression and paranoid ideation were signifi cant predictors of AUD (p < .05), and consequently were included in the model. As of the CUD model, preliminary analyses indicated that anxiety, psychoticism, paranoid ideation, obsessivecompulsive, hostility, depression, interpersonal sensitivity, phobic anxiety and the interaction between obsessive-compulsive and sex, hostility and sex, interpersonal sensitivity and sex, and hostility and obsessive-compulsive were signifi cant predictors (p < .05). Consequently, they were all included in the CUD model. Results from logistic regression model for AUD (Negelkerke R2 = .044) indicate that a positive diagnosis of obsessive-compulsive disorder and phobic anxiety were signifi cant predictors of AUD. As of the CUD model (Negelkerke R2 = .078), depression and the interaction between hostility and obsessive-compulsive were signifi cant predictors of CUD. Discussion To our knowledge, no previous study has evaluated sex differences in comorbidity of SUD and MHD among Spanish adolescents. Our results indicate that boys present with signifi cantly more substance use problems and disorders, whereas girls reported signifi cantly more mental health problems. Comorbidity between MHD and SUD was also signifi cantly higher among girls. In our study, no signifi cant sex differences were found in the frequency of alcohol drinking or intoxication, in line with previous research with Spanish adolescents (Prieto-Ursúa et al., 2020). Only a signifi cantly higher number of boys reported using cannabis in the last month compared to girls. These trends are in line with current national data (Plan Nacional Sobre Drogas, 2019). However, the prevalence of AUD and CUD was signifi cantly higher in boys than in girls, in line with previous studies (Duncan et al., 2015; Goldstein et al., 2012). Moreover, and among users, alcohol and cannabis-related problems were signifi cantly higher in boys that in girls. Previous studies have indicated that men are more likely to be hazardous drinkers (Erol & Karpyak, 2015), and that early Table 2 Prevalence (%) of positive cases by sex in the Brief Symptom Inventory dimensions among adolescents with AUD and CUD Alcohol Use Disorder (AUD) Cannabis Use Disorder (CUD) Boys (%) n = 121 Girls (%) n = 65 χ2 p Effect size Boys (%) n = 53 Girls (%) n = 13 χ2p Effect size Anxiety 28.1 34.4 0.499 .480 .065 30.2 50.0** * .310 .162 Somatization 21.5 43.1 8.547 .003 .227 24.5 53.8 * .050 .254 Psychoticism 19.0 24.6 0.500 .480 .066 26.4 46.2 * .190 .171 Paranoid 5.8 16.9 4.795 .029 .163 9.4 30.8 * .067 .247 OCD 19.0 29.2 1.977 .160 .117 24.5 69.2 * .006 .377 Hostility 10.7 33.8 13.300 ≤.001 .282 13.2 61.5 * .001 .459 Depression 20.7 20.0 0.000 1.000 -.008 30.2 38.5 * .741 .071 Interpersonal Sensitivity 5.0 10.8 * .226 .109 7.5 46.2 * .003 .428 Phobic Anxiety 30.6 43.1 2.382 .123 .125 35.8 61.5 1.886 .170 .208 GSI 4.1 7.7 0.470 .323 .075 5.7 38.5 * .006 .400 Note: OCD: Obsessive-Compulsive Disorder; GSI: Global Severity Index *Fisher exact test ** n = 12 due to missing values Table 3 Logistic regression model showing mental health dimensions signifi cantly predicting the presence of Alcohol Use Disorders among adolescents B Df p OR CI 95% Depression .968 1 .004 2.631 1.374 5.040 Hostility * OCD 1.179 1 .004 3.252 1.450 7.292 Table 4 Logistic regression model showing mental health dimensions signifi cantly predicting the presence of Cannabis Use Disorders among adolescents B Df p OR CI 95% OCD .671 1 .007 1.957 1.202 3.186 Phobic Anxiety .517 1 .013 1.677 1.116 2.520 Sergio Fernández-Artamendi, Víctor Martínez-Loredo, and Carla López-Núñez 40 drinking is more associated with problem drinking in males (Tedor et al., 2018), for whom drinking is more closely associated with negative consequences such as aggression (Gussler-Burkhardt & Giancola, 2005). On the other hand, women have shown to be less likely to engage in problem drinking (Erol & Karpyak, 2015). Similar results have been reported on cannabis use, since girls present with more protective factors than men that prevent them from escalating their cannabis use (Butters, 2004). Finally, and regarding mental health, world reports from the World Health Organization (WHO, n.d.) concludes that rates of depression, anxiety and somatic complaints are higher among women. Our results show a similar trend since girls reported signifi cantly higher scores in somatization, obsessive-compulsive symptomatology and depression, and also in paranoid ideation and overall global severity. Among adolescents with AUD, girls presented with higher rates of comorbidity than boys in all areas, in line with previous studies (Goldstein et al., 2012; Robert et al., 2007). However, according to our results, only the prevalence of somatization, hostility and paranoid ideation was signifi cantly higher among girls with AUD than among boys with AUD. Higher rates of somatization among young female heavy drinkers have already been reported (Laukkanen et al., 2001; Milani et al., 2004). Also, drinking among women has been linked to masculinity and aggression (PatróHernández et al., 2019), which could be ultimately related to the high levels of hostility found in our study. Moreover, girls have shown higher sensitivity (Erol & Karpyak, 2015; Salvatore et al., 2017) and vulnerability to alcohol effects and their interpersonal consequences (Chandley et al., 2014; Presley & Pimentel, 2006). Drinking among women goes against traditional gender norms (Fernández-Rodríguez et al., 2019), making it is less socially acceptable for them (Harrison & Esqueda, 2000). Consequently, alcohol use among women is associated with increased social and personal stigma (da Silveira et al., 2018) and might be linked to additional mental health problems. As of paranoid ideation, previous studies have also reported high levels of paranoid ideation among women with SUD (Newland et al., 2015), which the authors link to possible symptoms of anxiety and untreated withdrawal symptoms. However, further studies are required that confi rm this hypothesis. As of CUD, rates of comorbidity are also higher among girls in all areas. However, only the prevalence of obsessive-compulsive disorder, hostility, interpersonal sensitivity and global severity resulted signifi cantly higher among girls. Effect sizes indicate a moderate effect, which might refl ect a considerable clinical relevance of these sex differences, with a more severe profi le of mental health problems among girls that among boys with CUD. Our results are in line with previous research indicating that cannabis use is more strongly linked to aggressiveness and conduct problems in girls than in boys (Pedersen et al., 2001). Again, cannabis use has been commonly associated with male typicality and traditional male gender norms, whereas it goes against traditional female roles (Hemsing & Greaves, 2020). Moreover, these authors conclude that cannabis use is associated with aggressive masculinity among girls. These results might explain the higher levels of hostility and interpersonal sensitivity found in our sample of girls with CUD. Finally, the association between OCD and CUD had already been reported (Spradin et al., 2017), and CUD might emerge as a consequence of an excessive use of cannabis as a coping mechanism against intruding thoughts. In our study, the high rates of comorbidity between OCD and CUD among girls suggests that young female adolescents might be more vulnerable to this association. However, these hypotheses still require further research. Finally, and according to logistic regression models, depression and the interaction between obsessive-compulsive disorder and hostility increased three-fold the likelihood of presenting an AUD. These results would confi rm previous associations reported between high-risk drinking patterns, alcohol abuse and depression (Chhoa et al., 2019; Low et al., 2008; Ritcher et al., 2016). Previous studies have also reported a signifi cant association between externalizing problems and drinking (Colder et al., 2013; Colder et al., 2017; Strandheim et al., 2011). Interestingly, according to our results, externalizing problems represented by hostility (which includes irritability, urges to break things, arguments and outburst of temper) would be a risk factor only when interacting with internalizing problems such as intrusive thoughts of OCD. It could be that alcohol use can become problematic when drinking is used to deal with intrusive thoughts in an impulsive manner among these adolescents. This is of great clinical relevance given that comorbidity between AUD and OCD has shown specifi c associated risks such as suicidal thoughts (Gentil et al., 2009). Regarding CUD, logistic regression indicates that obsessivecompulsive disorder and phobic anxiety increased nearly two-fold the likelihood of presenting a CUD. These results corroborate the results by Spradlin et al. (2017), who fi nd a specifi c association between OCD and cannabis misuse. Additionally, our results are in line with the results from the meta-analyses by Kedzior and Laeber (2014), linking anxiety and cannabis use disorder. However, in our study, this association was specifi c only to phobic anxiety, which includes fear of crowds, public spaces and transports. It has been reported that cannabis users have diffi culties and present with evasive styles when coping with anxiety (Wilcockson & Sanal, 2016), and that social anxiety and avoidance are closely related with coping motives for cannabis use (Buckner & Zvolensky, 2014), which is in turn linked to cannabis dependence (Johnson et al., 2010). Further studies should corroborate these associations. Surprisingly, and despite the sex differences found in the bivariate analyses, no signifi cant interactions between sex and mental health problems have resulted signifi cant in the logistic regression models. This suggests that additional variables, not included here, might be mediating the sex differences detected in the association between MHD and SUD. The present study has several limitations. Firstly, this is a secondary analysis of a previous research, and epidemiological data might not be up to date with most current trends. Also, no data could be collected regarding additional sociodemographic variables that could infl uence the evaluated relationships. However, and given the considerable necessity of evaluating comorbidity between substance use and mental health, particularly among Spanish adolescents, as well as of improving our knowledge on sex differences in this regard, the present results are of great interest. Secondly, only alcohol and cannabis use patterns, problems and disorders have been thoroughly evaluated in our study. Further research should address comorbidity of additional substances and SUD, such as tobacco, the second most used substance by this population. The use of these substances could have additional impacts on the results of the relationships analyzed in this study. Besides, our study did not analyze the effect of possible comorbidities in mental health dimensions, neither comorbidities in substance use disorders. Sex Differences in Comorbidity Between Substance Use and Mental Health in Adolescents: Two Sides of the Same Coin 41 Further studies are necessary that address these issues. Thirdly, screening tests have been used to evaluate MHD. Although this has allowed us to carry out a comprehensive evaluation of multiple MHD, conclusions on the rates of comorbidity for the reported diagnoses have to be interpreted with caution. Finally, the crosssectional nature of our study prevents us from discussing possible causality in the reported associations. Despite boys presenting more alcohol and cannabis-related problems, as well as higher prevalence of AUD and CUD, girls reported signifi cantly more mental health problems and higher comorbidity between MHD and SUD. In particular, depression and the interaction between hostility and obsessive-compulsive symptoms indicated a higher risk of AUD, whereas obsessivecompulsive symptoms and phobic anxiety increased the risk of presenting CUD. Further studies should continue evaluating the associations between SUD and MHD and symptoms in adolescents, focusing on sex differences. Our study stresses the importance of addressing mental health problems among adolescents presenting with substance use problems and disorders, in order to provide a comprehensive psychological assistance. Particularly, special attention needs to be placed on adolescent girls, who present with signifi cantly more comorbid mental health problems. Finally, our results indicate that providing appropriate mental health care services and prevention programs to adolescents could contribute to reduce substance use problems in this population. Acknowledgement This study was funded by the Spanish Ministry of Innovation and Science (Ref: MICINN-08-PSI2008-00309). The authors would like to thank the Education Department of the Principality of Asturias, as well as the participating institutions, their staff and their students. 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