BRIEF RESEARCH REPORT published: 31 May 2019 doi: 10.3389/fpsyt.2019.00343 Mood Disorders and Severity of Addiction in Alcohol-Dependent Patients Could Be Mediated by Sex Differences Raul F. Palma-Álvarez 1,2, Laia Rodríguez-Cintas 1,2, Alfonso C. Abad 1, Marta Sorribes 1, Elena Ros-Cucurull 1,2, María Robles-Martínez 3, Lara Grau-López 1,2, Lourdes Aguilar 4 and Carlos Roncero 4* 1Addiction and Dual Diagnosis Unit, Department of Psychiatry, Vall d’Hebron University Hospital–Public Health Agency, Barcelona (ASPB), CIBERSAM, Barcelona, Spain, 2 Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain, 3 Institut de Neuropsiquiatria i Addiccions, Hospital del Mar, Barcelona, Spain, 4 Psychiatry Service, Salamanca University Health Care Complex, Institute of Biomedicine, University of Salamanca, Salamanca, Spain Edited by: Marc N. Potenza, Yale University, United States Background: Alcohol dependence is highly prevalent in the general population; some Reviewed by: differences in alcohol use and dependence between women and men have been Carolina Haass-Koffler, described, including outcomes and ranging from biological to social variables. This study Brown University, United States aims to compare the severity of alcohol dependence with clinical and psychopathological Kai Müller, Johannes Gutenberg characteristics between sexes. University Mainz, Germany Methods: A cross-sectional descriptive study was conducted in alcohol-dependent *Correspondence: outpatients; the recruitment period was 7 years. The assessment of these patients was Carlos Roncero croncero@saludcastillayleon.es carried out by obtaining sociodemographic characteristics and using the Semi-structured Clinical Interview for Axis I and II (SCID-I and SCID-II), European version of the Addiction Specialty section: Severity Index (EuropASI), Beck Depression Inventory (BDI), and State–Trait Anxiety This article was submitted to Addictive Disorders, Inventory (STAI) scales. Variables were compared and analyzed. a section of the journal Frontiers in Psychiatry Results: The sample was composed of 178 patients (74.2% males and 25.8% females) Received: 17 September 2018 with a mean age of 46.52 ± 9.86. No sociodemographic differences were found between Accepted: 01 May 2019 men and women. Females had a higher rate of suicide attempts and depression Published: 31 May 2019 symptoms at the treatment onset. When results of EuropASI were compared, females Citation: had worse psychological and employment results than males. According to consumption Palma-Álvarez RF, Rodríguez-Cintas L, Abad AC, variables, males had an earlier onset of alcohol use, had more regular alcohol use, and Sorribes M, Ros-Cucurull E, develop alcohol dependence earlier than females. Robles-Martínez M, Grau-López L, Aguilar L and Roncero C (2019) Conclusions: According to results, there are sex-dependent differences (severity and Mood Disorders and Severity of other variables such as mood or suicide) in alcohol dependence. Thus, this may implicate Addiction In Alcohol-Dependent Patients Could Be Mediated the need of future specific research and treatment programs based on the specific by Sex Differences. necessities of each sex. Front. Psychiatry 10:343. doi: 10.3389/fpsyt.2019.00343 Keywords: alcohol, dependence, depression, suicide attempts, severity, sex differences, gender Frontiers in Psychiatry | www.frontiersin.org 1 May 2019 | Volume 10 | Article 343 Palma-Álvarez et al. Sex Differences on Alcohol Dependence INTRODUCTION stage of the disorder. On the other hand, it is affirmed that women utilize and adhere to specialized resources in alcohol addiction Alcohol dependence is a worldwide problem highly prevalent and and they achieve better outcomes overall (14, 36, 40). They also associated with high morbidity and mortality (1–3). A total of 63.5 react positively to the consumption information (16). Thus, it million people around the world had alcohol dependence in 2015 would be helpful to thoroughly analyze the clinical differences (3), and globally, the age-standardized rate for alcohol dependence due to the presence of mixed results in previous studies and the is 843.2 per 100,000 people (3). For Western Europe, alcohol progressive changes observed in consumption patterns by sex. dependence seems to be higher, the rate being approximately 880.7 Furthermore, studies on this issue have been scarcely developed per 100,000 people (3). In Spain, 5% of the population aged between in Spain populations, especially if it is taking into account that 15 and 64 years have a risk consumption of alcohol (4). It is important not all studies have been performed with large samples and with to highlight that the prevalence of high-risk drinking is higher in validated scales and measures. men than in women (5), and in Europe, this sex difference is also This study aims to compare the clinical and psychopathological presented, reporting that 5.4% of men are alcohol-dependent as features and the addiction severity according to sex in Spanish opposed to 1.5% of women (6). Additionally, alcohol consumption alcohol-dependent patients. It is hypothesized that sex differences among women is increasing and sex differences are becoming in severity and in clinical and sociodemographic features will increasingly close, especially in the younger groups (7–10). be found. Sex could be a modulating factor for several issues in mental and addictive disorders (11–13). Specifically in alcohol dependence, men have early onset of alcohol use, have higher craving levels, METHODS and consume more alcohol than women (5, 14, 15), but in contrast, women have a lower tolerance even with an equal alcohol blood This descriptive study was developed by the Addiction and Dual level (16). Furthermore, women have more psychiatric comorbidity Diagnosis Unit of the Department of Psychiatry of Vall d’Hebron associated with alcohol consumption (17, 18), more medical and University Hospital of Barcelona between March 2007 and July 2014. neurological problems related to consumption and dependence (7, The study was approved by Ethical Committee of Vall d’Hebron 12, 19), and higher mortality rates (2, 19, 20). Although women University Hospital according to the Declaration of Helsinki. start consuming the substance later, they become dependent faster than men (7). In the light of the foregoing, this is related to the telescope effect, which refers to a faster course of the addictive Participants disorder among women (7, 21–23). It has been postulated that Those subjects who were seeking for a new substance use disorder biological differences could support this hypothesis (9, 13, 17, 23). treatment at the Addiction and Dual Diagnosis Unit were invited The telescope effect has also been described in alcohol-dependent to participate. The inclusion criteria were as follows: being over 18 patients with polydrug abuse (15, 24). years old, being in outpatient treatment for alcohol dependence, Deepening more on alcohol consumption and mental health and having signed the informed consent form that was approved issues, it has been described that alcohol-dependent women by the ethics committee of the hospital. The exclusion criteria have more psychiatric comorbidity and tend to present a higher were as follows: having a current dependence to other substances prevalence of anxiety and depressive symptoms and other mood (excluding nicotine) and inability of the patient to participate in disorders (18, 25–28). Depression may be an important factor the evaluation process (because of intoxication, current serious during the approaching of alcohol use disorder because it could psychiatric or somatic problems, and cognitive impairment or be a predictor factor related to treatment outcome, as it may be language barrier) at the time of the interviews. Patients did not associated with craving and alcohol relapse (29–31). Also, lower receive financial compensation for their participation. baseline level in depression is associated with better treatment compliance (32) and better therapy response (33). Besides, depression is frequently associated with suicidal behavior in Procedures The patients had one psychiatrist visit and four psychological patients with substance use disorders (34). A recent meta-analysis evaluation visits carried out by trained psychologists. on more than 400,000 participants reported a strong association Sociodemographic data, clinical information, and addiction between alcohol use disorder and suicidal behavior (35), and if it variables were collected during the psychiatrist’s visit, while data is analyzed as sex differences, women with alcohol use disorder related to addiction severity, presence of axis I and axis II mental have more suicidal attempts than men (36). disorders, depressive symptoms, anxiety symptoms, and suicidal Finally, it has been described that there are sex differences behavior were collected during the psychologists’ visits. in the difficulty of access to the clinical resources specialized in addictions between men and women (27, 37). These differences are due to several factors, such as social stigma, feelings of Evaluation Instruments shame, denial, fear of losing their children, lack of specialized resources, and lower purchasing power (38, 39) These conditions • Sociodemographic and clinical questionnaire: An ad hoc could have overestimated the higher prevalence among men and questionnaire that assesses sociodemographic variables, would mean that the groups of women studied were more serious including age, marital status, education, employment, because of the fact that they seek treatment in a more advanced clinical relevant variables. Frontiers in Psychiatry | www.frontiersin.org 2 May 2019 | Volume 10 | Article 343 Palma-Álvarez et al. Sex Differences on Alcohol Dependence • European version of the Addiction Severity Index (EuropASI): was conducted using sex as dependent variable. Statistically Semi-structured interview, which measures the severity of significant variables obtained after bivariate analysis were chosen addiction in different areas: medical, employment, alcohol as independent variables. The statistical program used was the consumption, use of other drugs, legal problems, family SPSS version 20. and social relationships, and psychological state. Scores range from 0 to 1; higher scores indicate higher severity (41). • Semi-structured Clinical Interview for Axis I and II (SCID-I RESULTS and SCID-II): These interviews were performed for evolution of Axis I and II disorders from the Diagnostic From an initial sample of 844 patients under alcohol dependence and Statistical Manual of Mental Disorders fourth edition treatment, the subgroup of patients with other substance (DSM-IV) (42, 43) . dependence (except nicotine) was excluded in order to obtain • Beck Depression Inventory (BDI): Self-administered questionnaire a more homogeneous sample. A total of 325 patients were that measures the severity of current depressive symptoms (44). selected, and from this group, only 178 patients completed the • State–Trait Anxiety Inventory (STAI): Self-administered evaluation process (74.2% men vs. 25.8% women; see Figure 1). questionnaire that measures the current anxiety symptoms of The mean age at the first contact in our unit was 46.52 ± 9.86. the patient (45). Previously, we ensured that there were no significant differences between sexes regarding the antecedent of previous treatments in other clinical centers. In our sample, women seek treatment Data Analysis at an age equal to or greater than men. A descriptive analysis was conducted. In order to compare mean It is observed that women present more depressive symptoms values between men and women, Student’s t test for quantitative (measured with BDI) at the beginning of the treatment. No variables and chi-square test for categorical variables were differences were found on nicotine use. Regarding the other used. Adjustment of the results by Bonferroni correction was sociodemographic and clinical variables, no differences were performed. A logistic regression analysis with forward selection found between men and women (Table 1). FIGURE 1 | Sample flowchart. Frontiers in Psychiatry | www.frontiersin.org 3 May 2019 | Volume 10 | Article 343 Palma-Álvarez et al. Sex Differences on Alcohol Dependence TABLE 1 | Demographic, clinical, and psychiatric variables and diagnoses of the sample. DEMOGRAPHIC VARIABLES N = 178 Men (n = 132) Women (n = 46) t p Mean ± SD Mean ± SD Mean ± SD AGE 46.52 ± 9.86 45.84 ± 9.73 48.48 ± 10.09 1.57 0.119 CIVIL STATUS % % % χ2 p Single 26.19 29.13 17.07 4.98 0.173 Married/partnered 34.52 33.07 39.02 Separated/divorced 37.5 37 39.02 Widow 1.78 0.79 4.88 LIVING WITH % % % χ2 p Partner and children 14.81 14.52 15.79 12.69 0.123 Partner 14.81 11.29 26.31 Children 7.41 3.23 21.05 Parents 14.81 24.2 10.53 Family 9.88 9.68 10.53 Friends 1.23 1.61 – Alone 22.22 24.19 15.79 Protected environment 6.17 8.06 – Unstable 2.47 3.23 – ACADEMIC LEVEL % % % χ2 p Primary (or lower) 43.6 45.9 36.6 1.083 0.364 Secondary (or upper) 56.4 54.1 63.4 EMPLOYMENT % % % χ2 p Active 27.22 30.71 16.67 3.141 0.076 CLINICAL VARIABLES % % % χ2 p Psychiatric history 51.92 52.5 50 0.046 0.830 Nicotine use 76.3 79.2 67.7 1.593 0.222 Psychotic symptoms 18.5 22.7 7.3 4.696 0.034 Suicide attempts 19.1 12.7 34.6 5.721 0.035 % % % χ2 p Medical history 59.4 59.2 60 1.254 0.534 Infectious Dis. 6.3 7 4.4 1.656 0.647 Cardiological Dis. 12.6 15.5 4.4 4.55 0.208 Hepatic Dis. 21.4 20.2 25 2.477 0.479 BDI 16.4 14.65 20.54 2.844 0.006* STAI-E 58.19 58.11 58.47 0.059 0.953 SCID I (111/39) % % % χ2 p Mood Disorder 30.7 26.4 42.5 3.592 0.072 Anxiety Disorder 17.1 14.3 25 2.386 0.144 SCID II % % % χ2 p Personality Disorder 19.2 20.7 15 0.620 0.492 *Significant with Bonferroni. All the significant results are in bold. TABLE 2 | Alcohol consumption chronologic features. N = 178 Men (n = 132) Women (n = 46) t p Mean SD Mean SD Mean SD Alcohol consumption in the last 13.14 13.30 14.5 14 8.83 9.84 2.61 0.011* 6 months, Standard Drinks (SD)/day Alcohol last month, SD/day 8.90 10.53 9.87 11.27 6.18 7.57 2.25 0.027 Age of first contact 16.06 5.42 15.37 4.294 18.12 7.55 2.94 0.004* Age at onset of regular consumption 24.97 10.36 22.57 8.543 31.95 12.02 4.73 0.000* Years of regular consumption 19.66 13.8 20.96 13.19 16.25 14.98 1.602 0.112 Years from the first contact to the 8.87 8.6 7.44 7.66 13.05 9.89 3.384 0.000* onset of dependence % % % χ2 p Abuse of other substance (DSM-IV) 19.5 22.5 11.6 2.345 0.174 *Significant with Bonferroni. All the significant results are in bold. Frontiers in Psychiatry | www.frontiersin.org 4 May 2019 | Volume 10 | Article 343 Palma-Álvarez et al. Sex Differences on Alcohol Dependence TABLE 3 | EuropASI subareas in the evaluation of the severity of addiction. N = 178 Men (n = 132) Women (n = 46) t p Mean SD Mean SD Mean SD Medical 0.31 0.35 0.29 0.35 0.39 0.37 1.74 0.084 Employment 0.53 0.33 0.49 0.33 0.63 0.3 2.46 0.015* Alcohol 0.37 0.31 0.37 0.31 0.36 0.31 0.31 0.761 Drugs 0.09 0.23 0.1 0.25 0.04 0.11 2.3 0.023* Legal 0.06 0.17 0.07 0.17 0.04 0.15 0.78 0.437 Familiar/Social 0.29 0.28 0.27 0.28 0.34 0.28 1.41 0.159 Psychological 0.33 0.23 0.3 0.23 0.4 0.21 2.47 0.015* *Significant with Bonferroni. All the significant results are in bold. TABLE 4 | Logistic regression analysis. in other countries (26, 29, 46, 47). It has been described that Wald p OR IC 95% depressive symptoms in alcohol-dependent women are related to a greater craving (which can lead to a relapse), and this Suicide attempts 4.903 0.027 15.500 1.370–17.538 BDI 8.779 0.003 1.055 1.018–1.093 issue has not been observed in the male sex (30, 31, 47, 48). Age at onset of 9.568 0.002 1.077 1.027–1.128 Therefore, depression becomes an important and critical issue regular consumption during the approaching for alcohol use disorder, not only for Employment 4.823 0.028 3.458 1.143–10.463 its prevalence but also because depression levels are associated Psychological 5.109 0.024 5.941 1.267–27.855 with some treatment outcomes (32, 33). Furthermore, depression All the significant results are in bold. and suicidal behavior are closely related; in the current sample, suicide behavior was significant at multivariate analysis. This is By comparing the variables related to the characteristics in line with some authors that have described that women with of consumption, men start drinking earlier, consume alcohol alcohol dependence are at higher risk for unplanned or planned regularly, and develop dependence earlier than women. When the attempts (49). Therefore, alcohol dependence is an important amount is observed, men consume more Standard Drinks per day risk factor for suicidal behavior, and this concern should always (1 SD = 10 g of alcohol in Spain) in the past 6 months (Table 2). be evaluated for an adequate and integral management (35, 36). It is observed that alcohol-dependent women had more problems Differences in relation to the presence of psychotic symptoms in the areas related to employment status and psychological state, between men and women are suggested, which would be which were measured by the EuropASI score (Table 3). However, consistent with previous studies that evaluate both the presence alcohol-dependent men showed more problems in the area of other of alcohol-induced psychotic symptoms and delirium tremens drug consumption (throughout life). (50, 51), but these results are nonsignificant when Bonferroni Finally, multivariate analysis is depicted in Table 4. There correction was performed. were statistically significant sex-dependent differences associated Although men consumed, in general, larger amounts of with suicide attempts, EuropASI (Psychological and Employment alcohol and began consumption earlier than women, taking areas), age at onset of regular consumption, and BDI. into account the results of the EuropASI scale, it could be suggested that alcohol dependence was more serious in women because they had higher severity in two of the seven DISCUSSION areas measured by the EuropASI scale (Employment and Psychological areas) and less severity in one of the seven areas The obtained results show the existence of sex-related differences (Drugs area), showing no differences in the other areas. It in alcohol consumption in the Spanish population. Alcohol- is also observed that the employment area in EuropASI was dependent women who sought treatment in our center presented more affected in women. The improvement of economic a later drinking onset and consumed less amounts of alcohol and work conditions in women could be associated with an than men. However, they tended to seek treatment in our unit increased consumption of alcohol in women. Recent studies later than men and had more depressive symptoms. These results have found that changes in economic and work conditions are in line with previous research in other countries. In many could be contributing to the convergence in sex differences recent studies, it has been described that there is an increasing (8). Scores in the Psychological area were worse in women; prevalence of alcohol dependence among women (8–10), and this could be related to the depressive symptoms in this group. they have a more severe alcohol use disorder (2, 11, 12, 19). This finding is similar to other research that described that Regarding clinical variables, sex differences are observed. the Psychological area in EuropASI is worse in women in It was found that women who sought treatment for alcohol several settings, such as outpatient centers and therapeutic dependence presented more depressive symptoms at the communities (22, 52). Thus, analyzing all the results, in beginning of the treatment, which had been previously described the current sample, there seems to exist a certain degree of Frontiers in Psychiatry | www.frontiersin.org 5 May 2019 | Volume 10 | Article 343 Palma-Álvarez et al. Sex Differences on Alcohol Dependence telescope effect, in line with other research in similar samples ETHICS STATEMENT in other countries (7, 21, 23). This study should be analyzed regarding its limitations. Thus, The research was approved by Ethical Committee of Vall d’Hebron the transversal nature and the incomplete representation of University Hospital according to Declaration of Helsinki. all the alcohol-dependent patients become an important issue (participants who do not seek treatment or patients with mixed dependences). Furthermore, we did not analyze differences AUTHOR CONTRIBUTIONS regarding nicotine use, as this substance could be related to CR and LG-L designed the study. RP-A, LR-C, AA, MR-M, and psychopathology and sex differences. It is also possible that ER-C collected the sample. LR-C, MS, and MR-M performed the men who seek treatment tend to minimize or deny their psychological evaluation. RP-A, LR-C, LG-L, and LA conducted depressive symptoms. Finally, the recruitment period (2007– the analyses and prepared the data. AA, MS, MR-M, ER-C, and 2014) could generate outdated information; however, these data LA performed the literature review. RP-A, AA, ER-C, and LA could contribute to understand this issue in Spanish populations wrote the initial version of this manuscript. All authors edited, with alcohol use disorder and allow to compare future research on read, and approved the last version of this manuscript. this issue. On the other hand, the study was conducted in a large homogeneous sample of patients who are only alcohol-dependent in an outpatient treatment center. Consequently, the results are FUNDING representative of the clinical activity in a real clinical setting. The current results provide new information that has been This research did not receive any specific grant from funding scarcely explored in large samples in Spanish populations with agencies in the public, commercial, or not-for-profit sectors. alcohol use disorder. The increased presence of depressive symptoms and the greater severity of addiction make women ACKNOWLEDGMENTS a particularly vulnerable group. Thus, as other authors recommended, it could be suggested that it is necessary to consider We are grateful to our research team for their support, particularly the special clinical characteristics of women when planning the Dr. Ángel Egido, Dr. Nieves Martínez-Luna, Dr. Joan Alvarós, and treatments (7, 53, 54). Furthermore, regarding the results of Dr. Claudia Gutiérrez (psychiatrists); Dr. Constanza Daigre and Dr. this study, it seems to be advisable that the implementations of Marta Perea (psychologists); Miguel Ángel Cantillo (nurse); and programs to detect depressive symptoms and to prevent suicide, Carmen Simón (social worker). We are also grateful to Ms. Rosa Milne especially in alcohol-dependent women, are needed. (mental health nurse from the UK) who reviewed the grammar. REFERENCES 9. Alati R, Betts KS, Williams GM, Najman JM, Hall WD. Generational increase in young women’s drinking: a prospective analysis of mother-daughter dyads. 1. Kranzler HR, Soyka M. Diagnosis and pharmacotherapy of alcohol use JAMA Psychiatry (2014) 71:952–7. doi: 10.1001/jamapsychiatry.2014.513 disorder: a review. JAMA (2018) 320:815–24. doi: 10.1001/jama.2018.11406 10. Keyes KM, Grant BF, Hasin DS. Evidence for a closing gender gap in alcohol 2. Kendler KS, Ohlsson H, Sundquist J, Sundquist K. Alcohol use use, abuse, and dependence in the United States population. Drug Alcohol disorder and mortality across the lifespan: a longitudinal cohort and Depend (2008) 93:21–9. doi: 10.1016/j.drugalcdep.2007.08.017 co-relative analysis. JAMA Psychiatry (2016) 73:575–81. doi: 10.1001/ 11. Roncero C, Rodríguez-Cintas L, Egido A, Barral C, Pérez-Pazos J, jamapsychiatry.2016.0360 Collazos F, et al. The influence of medical student gender and drug use on 3. Peacock A, Leung J, Larney S, Colledge S, Hickman M, Rehm J, et al. the detection of addiction in patients. J Addict Dis (2014) 33:277–88. doi: Global statistics on alcohol, tobacco and illicit drug use: 2017 status report. 10.1080/10550887.2014.969600 Addiction (2018) 113(10):1905–26. [In Press] doi: 10.1111/add.14234 12. Vatsalya V, Liaquat HB, Ghosh K, Mokshagundam SP. McClain CJ. A review 4. Observatorio Español de la Droga y Toxicomanías (2017). Encuesta sobre on the sex differences in organ and system pathology with alcohol drinking. Alcohol y Drogas en Población General en España (EDADES 2015). Madrid: Curr Drug Abuse Rev (2016) 9:87–92. doi: 10.2174/1874473710666170125151 Delegación del Gobierno para el Plan Nacional sobre Drogas. Available 410 on: http://www.pnsd.msssi.gob.es/profesionales/sistemasInformacion/ 13. Zagni E, Simoni L, Colombo D. Sex and gender differences in central informesEstadisticas/pdf/INFORME_2015.pdf (accessed September 1, 2018). nervous system-related disorders. Neurosci J (2016) 2016:2827090. doi: 5. Erol A, Karpyak VM. Sex and gender-related differences in alcohol use 10.1155/2016/2827090 and its consequences: contemporary knowledge and future research 14. Bravo F, Gual A, Lligoña A, Colom J. Gender differences in the long-term considerations. Drug Alcohol Depend (2015) 156:1–13. doi: 10.1016/j. outcome of alcohol dependence treatments: an analysis of twenty-year drugalcdep.2015.08.023 prospective follow up. Drug Alcohol Rev (2013) 32:381–8. doi: 10.1111/ 6. Rehm J, Shield KD, Gmel G, Rehm MX, Frick U. Modeling the impact of dar.12023 alcohol dependence on mortality burden and the effect of available treatment 15. Buu A, Dabrowska A, Mygrants M, Puttler LI, Jester JM, Zucker RA. Gender interventions in the European Union. Eur Neuropsychopharmacol (2013) differences in the developmental risk of onset of alcohol, nicotine, and marijuana 23:89–97. doi: 10.1016/j.euroneuro.2012.08.001 use and the effects of nicotine and marijuana use on alcohol outcomes. 7. Ait-Daoud N, Blevins D, Khanna S, Sharma S, Holstege CP. Women and J Stud Alcohol Drugs (2014) 75:850–8. doi: 10.15288/jsad.2014.75.850 addiction. Psychiatr Clin North Am (2017) 40:285–97. doi: 10.1016/j. 16. Calafat A, Fernández-Hermida JR, Becoña E, Juan M, Duch M, Fernández psc.2017.01.005 del Rio E, et al. Blood alcohol level tests in nightlife recreational settings as a 8. Keyes KM, Li G, Hasin DS. Birth cohort effects and gender differences in preventive tool. Actas Esp Psiquiatr (2013) 41:10–6. alcohol epidemiology: a review and synthesis. Alcohol Clin Exp Res (2011) 17. Greenfield SF. Women and alcohol use disorders. Harv Rev Psychiatry (2002) 35:2101–12. doi: 10.1111/j.1530-0277.2011.01562.x 10:76–85. doi: 10.1080/10673220216212 Frontiers in Psychiatry | www.frontiersin.org 6 May 2019 | Volume 10 | Article 343 Palma-Álvarez et al. Sex Differences on Alcohol Dependence 18. García-Carretero MA, Novalbos-Ruiz JP, Robles-Martínez M, Jordán- 39. Jackson A, Shannon L. Barriers to receiving substance abuse treatment Quintero MA, O’Ferrall-González C. Psychopathological profile and among rural pregnant women in Kentucky. Matern Child Health J (2012) prevalence of dual pathology on patients with alcoholic dependence 16:1762–70. doi: 10.1007/s10995-011-0923-5 undergoing outpatient treatment. Actas Esp Psiquiatr (2017) 45:1–11. 40. DeVito EE, Babuscio TA, Nich C, Ball SA, Carroll KM. Gender differences 19. Milic J, Glisic M, Voortman T, Borba LP, Asllanaj E, Rojas LZ, et al. in clinical outcomes for cocaine dependence: randomized clinical trials of Menopause, ageing, and alcohol use disorders in women. Maturitas (2018) behavioral therapy and disulfiram. Drug Alcohol Depend (2014) 145:156–67. 111:100–9. doi: 10.1016/j.maturitas.2018.03.006 doi: 10.1016/j.drugalcdep.2014.10.007 20. Roerecke M, Rehm J. Alcohol use disorders and mortality: a systematic review 41. Kokkevi A, Hartgers C. European adaptation of a multidimensional and meta-analysis. Addiction (2013) 108:1562–78. doi: 10.1111/add.12231 assessment instrument for drug and alcohol dependents. Eur Addict Res 21. Zilberman M, Tavares H. el-Guebaly N. Gender similarities and differences: (1995) 1:208–10. doi: 10.1159/000259089 the prevalence and course of alcohol- and other substance-related disorders. 42. First MB, Spitzer RL, Gibbon M, Williams JB. Structured clinical interview J Addict Dis (2003) 22:61–74. doi: 10.1300/J069v22n04_06 for DSM-IV axis I disorders, clinician version (SCID-CV). Washington: 22. Hernandez-Avila CA, Rounsaville BJ, Kranzler HR. Opioid-, cannabis- American Psychiatric Press, Inc. (1997). and alcohol-dependent women show more rapid progression to substance 43. First MB, Gibbon M, Spitzer RL, Williams JB, Benjamin LS. Structured abuse treatment. Drug Alcohol Depend (2004) 74:265–72. doi: 10.1016/j. clinical interview for DSM-IV axis II personality disorders (SCID-II). drugalcdep.2004.02.001 Washington: American Psychiatric Press, Inc. (1997). 23. Randall CL, Roberts JS, Del Boca FK, Carroll KM, Connors GJ, Mattson ME. 44. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for Telescoping of landmark events associated with drinking: a gender comparison. measuring depression. Arch Gen Psychiatry (1961) 4:561–71. doi: 10.1001/ J Stud Alcohol (1999) 60:252–60. doi: 10.15288/jsa.1999.60.252 archpsyc.1961.01710120031004 24. Lewis B, Hoffman LA, Nixon SJ. Sex differences in drug use among 45. Gaudry E, Vagg P, Spielberger CD. Validation of the state–trait distinction polysubstance users. Drug Alcohol Depend (2014) 145:127–33. doi: 10.1016/j. in anxiety research. Multivariate Behav Res (1975) 10:331–41. doi: 10.1207/ drugalcdep.2014.10.003 s15327906mbr1003_6 25. Miquel L, Roncero C, García-García G, Barral C, Daigre C, Grau-López L, 46. Dişsiz M, Beji N, Oskay Ü. The effects of alcohol dependence on the quality et al. Gender differences in dually diagnosed outpatients. Subst Abus (2013) of life and sex life of women. Subst Use Misuse (2015) 50:1373–82. doi: 34:78–80. doi: 10.1080/08897077.2012.709223 10.3109/10826084.2015.1013129 26. Cornelius JR, Jarrett PJ, Thase ME, Fabrega H Jr, Haas GL, Jones-Barlock A, et al. 47. Petit G, Luminet O, Cordovil de Sousa Uva M, Monhonval P, Leclercq S, Gender effects on the clinical presentation of alcoholics at a psychiatric hospital. Spilliaert Q, et al. Gender differences in affects and craving in alcohol- Compr Psychiatry (1995) 36:435–40. doi: 10.1016/S0010-440X(95)90251-1 dependence: a study during alcohol detoxification. Alcohol Clin Exp Res 27. Limosin F. Clinical and biological specificities of female alcoholism. (2017) 41:421–31. doi: 10.1111/acer.13292 Encephale (2002) 28:503–9. 48. Robles-Martínez M, García-Carretero MÁ, Gibert J, Palma-Álvarez RF, Abad 28. Conner KR, Pinquart M, Gamble SA. Meta-analysis of depression and AC, Sorribes M, et al. Differences between craving and health-related quality substance use among individuals with alcohol use disorders. J Subst Abuse of life in patients with alcohol dependence with or without dual pathology in Treat (2009) 37:127–37. doi: 10.1016/j.jsat.2008.11.007 outpatient treatment: a descriptive study. Med Clin (Barc) (2018) 150:49–55. doi: 29. Abulseoud OA, Karpyak VM, Schneekloth T, Hall-Flavin DK, Loukianova 10.1016/j.medcli.2017.06.005 LL, Geske JR, et al. A retrospective study of gender differences in depressive 49. Conner KR, Hesselbrock VM, Meldrum SC, Schuckit MA, Bucholz KK, Gamble symptoms and risk of relapse in patients with alcohol dependence. Am J SA, et al. Transitions to, and correlates of, suicidal ideation, plans, and unplanned Addict (2013) 22:437–42. doi: 10.1111/j.1521-0391.2013.12021.x and planned suicide attempts among 3,729 men and women with alcohol 30. Luminet O, Cordovil de Sousa Uva M, Fantini C, de Timary P. The association dependence. J Stud Alcohol Drugs (2007) 68:654–62. doi: 10.15288/jsad.2007.68.654 between depression and craving in alcohol dependency is moderated by 50. Jordaan GP, Emsley R. Alcohol-induced psychotic disorder: a review. Metab gender and by alexithymia factors. Psychiatry Res (2016) 239:28–38. doi: Brain Dis (2014) 29:231–43. doi: 10.1007/s11011-013-9457-4 10.1016/j.psychres.2016.02.062 51. Soyka M, Raith L, Steinberg R. Mean age, sex ratio and psychopathology in 31. Zilberman ML, Tavares H, Hodgins DC. el-Guebaly N. The impact of gender, alcohol psychoses. Psychopathology (1988) 21:19–25. doi: 10.1159/000284535 depression, and personality on craving. J Addict Dis (2007) 26:79–84. doi: 52. De Wilde J, Broekaert E, Rosseel Y, Delespaul P, Soyez V. The role of gender 10.1300/J069v26n01_10 differences and other client characteristics in the prevalence of DSM-IV 32. Gjestad R, Franck J, Hagtvet KA, Haver B. Level and change in alcohol affective disorders among a European therapeutic community population. consumption, depression and dysfunctional attitudes among females treated for Psychiatr Q (2007) 78:39–51. doi: 10.1007/s11126-006-9025-8 alcohol addiction. Alcohol Alcohol (2011) 46:292–300. doi: 10.1093/alcalc/agr018 53. Gual A, Sabadini MB. Implementing alcohol disorders treatment throughout 33. Merrill JE, Reid AE, Carey MP, Carey KB. Gender and depression moderate the community. Curr Opin Psychiatry (2011) 24:203–7. doi: 10.1097/ response to brief motivational intervention for alcohol misuse among college YCO.0b013e3283459256 students. J Consult Clin Psychol (2014) 82:984–92. doi: 10.1037/a0037039 54. Rolland B, Paille F, Gillet C, Rigaud A, Moirand R, Dano C, et al. 34. Rodríguez-Cintas L, Daigre C, Braquehais MD, Palma-Alvarez RF, Grau- Pharmacotherapy for alcohol dependence: the 2015 recommendations of the López L, Ros-Cucurull E, et al. Factors associated with lifetime suicidal French Alcohol Society, issued in partnership with the European Federation of ideation and suicide attempts in outpatients with substance use disorders. Addiction Societies. CNS Neurosci Ther (2016) 22:25–37. doi: 10.1111/cns.12489 Psychiatry Res (2018) 262:440–5. doi: 10.1016/j.psychres.2017.09.021 35. Darvishi N, Farhadi M, Haghtalab T, Poorolajal J. Alcohol-related risk of Conflict of Interest Statement: The authors declare that the research was suicidal ideation, suicide attempt, and completed suicide: a meta-analysis. conducted in the absence of any commercial or financial relationships that could PLoS One (2015) 10:e0126870. doi: 10.1371/journal.pone.0126870 be construed as a potential conflict of interest. 36. Arnau MM. Differential features of female alcoholism. Adicciones (2010) 22:339–52. doi: 10.20882/adicciones.176 Copyright © 2019 Palma-Álvarez, Rodríguez-Cintas, Abad, Sorribes, Ros-Cucurull, 37. Schmidt L, Weisner C. The emergence of problem-drinking women as a Robles-Martínez, Grau-López, Aguilar and Roncero. This is an open-access article special population in need of treatment. Recent Dev Alcohol (1995) 12:309– distributed under the terms of the Creative Commons Attribution License (CC 34. doi: 10.1007/0-306-47138-8_20 BY). The use, distribution or reproduction in other forums is permitted, provided 38. Small J, Curran GM, Booth B. Barriers and facilitators for alcohol treatment the original author(s) and the copyright owner(s) are credited and that the original for women: are there more or less for rural women? J Subst Abuse Treat publication in this journal is cited, in accordance with accepted academic practice. No (2010) 39:1–13. doi: 10.1016/j.jsat.2010.03.002 use, distribution or reproduction is permitted which does not comply with these terms. Frontiers in Psychiatry | www.frontiersin.org 7 May 2019 | Volume 10 | Article 343