ORIGINAL RESEARCH published: 09 April 2021 doi: 10.3389/fpsyt.2021.659063 Alexithymia in Patients With Substance Use Disorders and Its Relationship With Psychiatric Comorbidities and Health-Related Quality of Life Raul F. Palma-Álvarez 1,2,3,4*, Elena Ros-Cucurull 1,2,3,4 , Constanza Daigre 1,2,3,4 , Marta Perea-Ortueta 1,3 , Pedro Serrano-Pérez 1,2,3 , Nieves Martínez-Luna 1 , Anna Salas-Martínez 1 , María Robles-Martínez 5,6 , Josep A. Ramos-Quiroga 1,2,3,4 , Carlos Roncero 7,8 and Lara Grau-López 1,2,3,4 1 Department of Psychiatry, Hospital Universitari Vall d’Hebron, Barcelona, Spain, 2 Department of Psychiatry and Legal Edited by: Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain, 3 Group of Psychiatry, Mental Health and Addiction, Vall Luigi Janiri, d’Hebron Institut de Recerca (VHIR), Barcelona, Spain, 4 Biomedical Network Research Centre on Mental Health Catholic University of the Sacred (CIBERSAM), Barcelona, Spain, 5 Institute of Neuropsychiatry and Addictions (INAD), Parc de Salut Mar, Barcelona, Spain, Heart, Italy 6 Hospital del Mar Institute for Biomedical Research (IMIM), Barcelona, Spain, 7 Psychiatry Service, University of Salamanca Reviewed by: Health Care Complex, Insitute of Biomedicine, Salamanca, Spain, 8 Psychiatry Unit, School of Medicine, University of Fengchun Wu, Salamanca, Salamanca, Spain Guangzhou Medical University, China Saeed Ahmed, Rutland Regional Medical Center, Background: Alexithymia frequently correlates with several psychiatric disorders, United States including substance use disorder (SUD). However, most studies reporting the *Correspondence: associations between alexithymia and psychiatric disorders have been performed in Raul F. Palma-Álvarez populations without SUD. This research, therefore, evaluates alexithymia in Spanish rpalma@vhebron.net patients with SUD and the relationship among alexithymia, psychiatric comorbidities, Specialty section: psychological symptoms/traits, SUD variables, and health-related quality of life (HRQoL). This article was submitted to Addictive Disorders, Methodology: A cross-sectional study was conducted with 126 Spanish outpatients a section of the journal with SUD (75.4% males; mean age 43.72 ± 14.61 years), correlating their alexithymia Frontiers in Psychiatry levels (using the Toronto Alexithymia Scale 20 [TAS-20]) to their psychiatric comorbidities, Received: 26 January 2021 psychological symptoms/traits, SUD variables, and HRQoL. Accepted: 15 March 2021 Published: 09 April 2021 Results: Alexithymia was significantly higher in patients who had cannabis use disorder. Citation: Higher alexithymia scores were also related to higher levels of depression, anxiety, Palma-Álvarez RF, Ros-Cucurull E, Daigre C, Perea-Ortueta M, impulsivity, and lower HRQoL. After multivariate analysis, trait anxiety, impulsivity, and Serrano-Pérez P, Martínez-Luna N, the physical component summary of the HRQoL were found to be independently related Salas-Martínez A, Robles-Martínez M, to alexithymia. Ramos-Quiroga JA, Roncero C and Grau-López L (2021) Alexithymia in Conclusions: SUD patients with higher alexithymia levels have more frequently Patients With Substance Use Disorders and Its Relationship With psychiatric comorbidities, present specific psychological features, and have worse Psychiatric Comorbidities and HRQoL. Hence, it is important to evaluate these factors and offer more accurate Health-Related Quality of Life. psychotherapeutic approaches for this patient population. Front. Psychiatry 12:659063. doi: 10.3389/fpsyt.2021.659063 Keywords: alexithymia, anxiety, depression, health-related quality of life, impulsivity, substance use disorder Frontiers in Psychiatry | www.frontiersin.org 1 April 2021 | Volume 12 | Article 659063 Palma-Álvarez et al. Alexithymia in Substance Use Disorders INTRODUCTION for psychosis (28, 34). Nevertheless, as far as we know, no specific study has been conducted concerning alexithymia in Substance use disorder (SUD) is a complex, multifactorial, SUD patients with schizophrenia or other psychotic disorders. and chronic disease that negatively influences on health, social However, it could be expected that alexithymia is related to and economic status (1, 2). Several mechanisms are implicated psychotic disorders in SUD patients, as it has already been in SUD pathogenesis, particularly emotional regulation issues, associated with cannabis or other substance use (7, 29) and as from both biological and clinical viewpoints (3–5). Alexithymia substance use is a risk factor for primary psychotic disorders is a multidimensional construct, and it is a key point in and substance-induced psychosis (35). In any case, as highlighted emotional processes, as emotional awareness and identification above, no specific manuscript on this issue has been published. are critical to regulating emotions (4, 6–8). Alexithymia involves A negative association has been reported between alexithymia four main dimensions: difficulty identifying and/or describing and health-related quality of life (HRQoL) in general and clinical feelings, difficulty differentiating feelings from bodily sensations, populations (36–38). However, this relationship has been scarcely a decrease in or absence of symbolic thinking, and an externally studied in the addiction field, as only two studies have been oriented cognitive style (9, 10). When analyzed as a categorical designed for this purpose. It is, therefore, generally believed trait, in the general population, the prevalence of alexithymia that, in SUD patients, as in patients with other disorders, lower is estimated to be 6–10%, and, in SUD patients, it is estimated alexithymia levels mean better HRQoL (36, 38). to be 42–67% (7, 11–13). However, despite some controversies Finally, the association between alexithymia and psychiatric about whether alexithymia should be considered a categorical comorbidities in SUD patients has been scarcely studied in the or dimensional variable, the current literature states that it is Spanish population. Most research in this group has considered a normally distributed trait in the population, with a relative alexithymia with other psychiatric disorders, examined substance stability across the lifespan (8, 9, 14, 15). Alexithymia also consumption as a secondary variable, or included patients with seems to be a stable trait, independent of substance use or long periods of abstinence from substance use (39, 40). Also, to withdrawal (7, 16), although not all research supports this point our knowledge, no studies on the relationship between HRQoL (17). Some studies suggest that alexithymia is related to risky and alexithymia have been performed in Spanish SUD patients. substance use (18, 19), more severe addictions (20), higher This point has a crucial importance as alexithymia is a valid cross- craving levels (21), and more treatment dropouts/relapses (7). cultural construct but with level differences among cultures (8), Additionally, alexithymia seems to be related to family history and hence, comparisons on this issue among different cultures of alcohol dependence (22). Finally, it is important to note shed light on understanding alexithymia in clinical practice. that alexithymia may interfere with treatment aims, especially Therefore, this study evaluates alexithymia in Spanish SUD in emotional and insight-oriented therapies (11, 23, 24). SUD outpatients and the relationship among alexithymia, psychiatric patients with higher alexithymia levels may have more problems comorbidities, psychological symptoms/traits, SUD variables, in engaging psychotherapeutic treatments and would form and HRQoL. We hypothesize that SUD patients with higher weaker therapeutic alliances (24, 25). However, not all researchers alexithymia levels will exhibit more psychiatric comorbidities, conclude that alexithymia is related to SUD outcomes (5, 7, 26), more anxiety and depression, and worse HRQoL values. and hence, it is important to conduct more research on this issue. Alexithymia is frequently related to psychiatric disorders, METHODS including SUD, psychosis, anxiety, and depressive disorders (10, 27, 28). Most studies reporting associations between A cross-sectional study was conducted in an outpatient addiction alexithymia and psychiatric disorders have been performed in treatment center in Barcelona, Spain. SUD patients who sought populations without SUD, even though psychiatric comorbidities treatment between January 2018 and January 2019 were included. are frequently observed in SUD patients (1, 23, 24, 27, 28). This study was approved by the Hospital Ethics Committee Nonetheless, as in the studies performed in populations without according to the World Medical Association’s Declaration of SUD, the limited clinical research that is available states that Helsinki. Sampled patients received no financial compensation alexithymia may be related to several psychiatric disorders for participating. in SUD patients (11, 19, 29, 30). In any case, the role of To be included in the study, patients were required to: be alexithymia in SUD is not well-established, especially regarding over 18 years of age, have Spanish nationality, meet SUD criteria how comorbidities are related to SUD in those patients with according to the Diagnostic and Statistical Manual of Mental alexithymia (7). On one hand, some authors argues that Disorders Fifth Edition (DSM-5) (41), be actively consuming alexithymia may partially predict the presence of anxiety and substances, and understand and sign the written informed depression in alcohol-dependent patients (7, 30). On the other consent document prior to participation. Patients were excluded hand, other authors propose that depression could lead to alcohol if they were cognitively impaired, were acutely intoxicated, dependence in patients with alexithymia (31). Personality traits presented language barriers, or were currently involved in a and disorders have also been associated with higher levels of pharmacological clinical trial. Note that cognitive impairment alexithymia in SUD patients (32), and the relationship between was evaluated by two ways: the first one by assessing the alexithymia and primary psychotic disorders (e.g., schizophrenia) clinical history of any cognitive impairments, and the second is relatively well-documented (33). It has been proposed that one by clinical assessment and by using Mini-Mental State alexithymia may predict psychotic experiences or be a risk factor Examination (≥27). Therefore, participants with previous history Frontiers in Psychiatry | www.frontiersin.org 2 April 2021 | Volume 12 | Article 659063 Palma-Álvarez et al. Alexithymia in Substance Use Disorders of cognitive impairment or with a cognitive impairment detected - The Dickman Impulsivity Inventory (DII): This 23-item, self- at the first visit were excluded. Patients who were acutely reported instrument evaluates functional and dysfunctional intoxicated during their first appointment were invited to impulsivity (50). participate in the second meeting. Regarding language barriers, - Toronto Alexithymia Scale 20 (TAS-20): This self-reported and according to study aims, all patients had to speak Spanish instrument is considered the “gold standard” for alexithymia since validated instruments in their Spanish version were used evaluation, and it has demonstrated its reliability and validity (see below). in several cultures and languages (8, 9, 14, 51). The TAS- The evaluation process consisted of four visits conducted 20 measures alexithymia across 20 items, rated from one by trained staff (psychiatrists and psychologists) during each to five. The sum of the ratings for those items generates patient’s 1st week at the outpatient center, concurrent with the a total score, and the higher the score, the higher the usual outpatient treatment. level of alexithymia. This scale has three subscales: difficulty in identifying feelings, difficulty in describing feelings, and externally oriented cognition (14, 51). The TAS-20 was not Measures developed to independently assess these three subscales but to - Sociodemographic, medical, psychiatric, and addiction-related consider them together, as a single measure (14). Some authors variables: An ad-hoc questionnaire was developed to gather analyze alexithymia as a dichotomous variable (alexithymia vs. and systematize the patients’ sociodemographic characteristics non-alexithymia) and use 61 points as cutoff value for this and their medical, psychiatric, and addiction-related variables. scale, but other researches recommend analyzing alexithymia - Psychiatric comorbidities: The Semi-Structured Clinical as a dimensional or spectrum trait (8, 9, 14). Therefore, Interview for Axis-I Disorders of the DSM-IV (SCID-I) and we decided to analyze each patient’s total TAS-20 score the Semi-Structured Clinical Interview for Axis-II Disorders (dimensional) and compare it to the other variables included of the DSM-IV (SCID-II) were used to assess patients’ in the research. psychiatric comorbidities (42). - Addiction severity: The European Addiction Severity Index Statistical Analyses (EuropASI) was employed to evaluate addiction severity, as it Descriptive, bivariate and multivariate analyses were performed. considers general consumption variables, legal problems, and The descriptive analysis involved measuring percentages, means, family/social relationships, as well as medical, occupational, medians, and standard deviations. The bivariate analysis psychological, and economic status (43, 44). The median for was subsequently performed using Student’s t-test, with the each component was used for the analysis. alexithymia score being evaluated for each variable. To - Beck Depression Inventory (BDI-I): This self-reported rating dichotomize some variables, we chose generally accepted cutoff inventory measures depression symptomatology (45, 46). points. Thus, the cutoff point for the BDI was 17 points or It classifies depression, according to points, as follows: no more, as scores >17 are clinically relevant for depression (45, depression (or normal mood): 1–10 points; mild mood 46), and the cutoff value for the SF-36 was set to 50 points disturbance: 11–16 points; borderline clinical depression: because, from 50 onward, patients exhibit better HRQoL. For the 17–20 points; moderate depression: 21–30 points; severe EuropASI, STAI, BIS-11, and DII measures, we chose the median. depression: 31–40 points; and extreme depression: more than Bonferroni correction was executed to reduce false positives. 40 points (45, 46). For analysis in this research, we grouped Finally, a multivariate analysis (linear regression) was performed the scores into patients with 1–16 points and those with 17+, via a stepwise method, including variables that retained statistical because, from 17 onwards, the score is clinically relevant. significance after the Bonferroni correction. All statistical tests - State-Trait Anxiety Inventory (STAI): This inventory is were two-sided, and a value of p < 0.05 was considered commonly used in clinical settings to measure anxiety (trait statistically significant. SPSS version 21 statistical software was and state) (47). employed in this project. - Health-related quality of life (HRQoL): The 36-Item Short Form Health Survey (SF-36) was used to measure functional RESULTS health and well-being from the patients’ perspectives (48). The SF-36 provides scores for eight domains (physical functioning, During the recruitment period, 204 patients began a new role limitations due to physical problems, bodily pain, general treatment process, but 78 were excluded for the following health perceptions, vitality, social functioning, role limitations reasons: no active substance consumption (n = 26), language due to emotional problems, and mental health), which can barriers (n = 21), and not agreeing to participate (n = 31). be aggregated into two summary measures: the physical Therefore, 126 patients met the inclusion criteria. Among these, component summary (PCS) and the mental component the mean age was 43.72 ± 14.61 years old (median 40), and summary (MCS). We used a cutoff value of 50 points, because, the sample contained 94 men (75.4%). The participants’ mean from this score onward, patients exhibit better HRQoL. TAS-20 score was 57.40 ± SD 12.98, and the prevalence of - Barratt Impulsivity Scale (BIS-11): This self-reported scale alexithymia was 41.3% (using 61 points as cutoff). No gendered measures “trait impulsivity” and provides a total score and differences were found. Regarding sociodemographic variables, three subscale scores: cognitive impulsivity, motor impulsivity, only coexistence and academic level were significantly related to and unplanned impulsivity (49). higher alexithymia levels (Table 1). Frontiers in Psychiatry | www.frontiersin.org 3 April 2021 | Volume 12 | Article 659063 Palma-Álvarez et al. Alexithymia in Substance Use Disorders TABLE 1 | Sociodemographic variables related to alexithymia levels. DISCUSSION Variable % Mean score of TAS-20 ± SD t p The current research provides new information on alexithymia in Age (years) SUD patients, especially on the relationship among alexithymia, (mean: 43.72 ± 14.61; psychiatric comorbidities, and psychological characteristics. We median: 40) found that SUD patients with cannabis use disorder, psychiatric <40 50 59.27 ± 13.24 1.773 0.079 comorbidities (especially mood and psychotic spectrum ≥40 50 55.52 ± 12.16 disorders), impulsivity, anxiety, or depressive symptoms have Sex higher alexithymia levels. These higher alexithymia levels were Males 75.4 56.80 ± 13.0 0.851 0.396 also related to worse HRQoL scores (particularly on PCS) in SUD Females 24.6 59.10 ± 12.95 patients. The prevalence of alexithymia and the TAS-20 mean Marital status score found in this research were similar to those determined in Married 40.7 56.50 ± 12.34 0.254 0.800 previous studies among SUD patients (7, 13, 21, 22) and were Other 59.3 57.11 ± 13.30 higher compared to general populations (7, 12). Coexistence Regarding current results, cannabis use disorder and Family 66.1 54.54 ± 11.59 2.128 <0.037* anxiety (particularly trait anxiety in the multivariate analysis) Other 33.9 60.26 ± 14.34 were significantly related to higher alexithymia levels. These Level of studies associations may be explained in several ways and the causality <8 years 86.8 57.62 ± 13.27 2.007 <0.047* association is beyond the current study due to the cross- ≥8 years 13.2 50.53 ± 8.08 sectional design. One explanation is that those associations Criminal records are independent, specifically that the mere trait anxiety Yes 38.1 55.95 ± 12.90 0.306 0.760 (independently of alexithymia) may be one of the most important predictors of cannabis use disorder (29). Another No 61.9 56.77 ± 13.57 explanation is that both alexithymia and anxiety could lead to * The result is statistically significant. substance use as a self-medication strategy for managing distress (7, 52). In this vein, Dorard et al. (29) propose that patients with alexithymia and anxiety may use cannabis as a stress-coping strategy (29). Finally, it has been described that alexithymia and Regarding substance use variables (Table 2), participants most SUD severity are important anxiety predictors (30). For all the often used alcohol (excluding tobacco), followed by cocaine and above, the current findings should be analyzed in longitudinal cannabis. Alexithymia levels were significantly higher in patients studies to evaluate better how alexithymia, anxiety, and SUD who had a history of cannabis use disorder. There were also interact and how they are associated. correlations between TAS-20 and worse EuropASI scores for the Intriguingly, however, anxiety spectrum disorders were not family/social and psychological items. correlated to alexithymia levels in this research; thus, the current Regarding psychiatric comorbidities and psychological results are in line with other authors, who assert that anxiety and variables (Table 3), SUD patients with psychiatric comorbidities SUD are related independently of any anxiety disorder. That is, had higher alexithymia levels, especially those affected by anxiety may be present transversally, as a symptom or trait in the mood disorder spectrum and the psychotic disorder SUD (26, 52). spectrum (clearly in substance-induced psychosis). Also, Closely connected to anxiety, depressive symptoms were some psychological traits were associated with higher significantly associated with higher alexithymia levels in the alexithymia scores, specifically depression (BDI), anxiety bivariate analysis. This finding was expected because alexithymia (STAI), and impulsivity (BIS-11; DII). Patients with higher is correlated with negative affects (16, 27, 29). It is important TAS-20 scores had worse HRQoL scores, with a statistical to highlight that depression does not influence the stability significance in all domains and component summaries (PCS of alexithymia scores in SUD patients (16, 17). Anxiety and and MCS). depressive symptoms could partially explain the impaired A multivariate analysis was performed using the variables psychological item on the EuropASI, as both factors have been that retained statistical significance after Bonferroni correction. correlated to this domain (26). Thus, in the current results, SUD The following variables were included in the linear regression: patients with higher alexithymia levels had more anxiety, more lifetime history of cannabis use disorder, EuropASI psychological depressive symptoms, and greater psychological impairments as domain, substance-induced psychosis, BDI, STAI, BIS-11 total measured by the EuropASI. score, DII dysfunctional impulsivity, and PCS and MCS Alexithymia and impulsivity imply several cognitive processes values from the SF-36. The linear regression (R2 = 0.397; and are key points, not only in emotional deregulation, but F = 10.296; p < 0.001) showed that trait anxiety according also in SUD (18, 53). We found a positive relationship between to STAI (Beta 2.740; t = 2.895; p = 0.006), BIS-11 total impulsivity and alexithymia in SUD patients, which could be score (Beta 3.745; t = 2.248; p = 0.029), and PCS (Beta expected because impulsivity and SUD are closely related (1). 3.861; t = 2.147; p = 0.037) were independently related Previous studies support these results. For example, Shishido to alexithymia. et al. (53) have found that alcohol-dependent patients with high Frontiers in Psychiatry | www.frontiersin.org 4 April 2021 | Volume 12 | Article 659063 Palma-Álvarez et al. Alexithymia in Substance Use Disorders TABLE 2 | Substance use related variables analyzed by comparing to mean scores of alexithymia. Lifetime history of substance use disorders % Mean score of TAS-20 ± SD t p Alcohol use disorder Yes 62.8 57.54 ± 13.36 1.040 0.301 No 37.2 54.77 ± 10.86 Cannabis use disorder Yes 60.6 60.81 ± 12.98 2.710 <0.008*,** No 39.4 53.72 ± 11.44 Cocaine use disorder Yes 61.7 57.09 ± 13.46 0.565 0.574 No 38.3 55.58 ± 10.89 Opioid use disorder Yes 21.3 58.70 ± 13.09 0.882 0.380 No 78.7 55.92 ± 12.36 Benzodiazepine use disorder Yes 19.2 60.94 ± 11.39 1.691 0.094 No 80.8 55.46 ± 12.59 Tobacco use disorder Yes 78.7 57.01 ± 12.32 0.749 0.456 No 21.3 54.65 ± 13.31 SUD severity according to EuropASI† Medical ≤0.18 54.60 ± 13.66 2.051 <0.043* >0.19 59.71 ± 12.43 Employment support status ≤0.56 55.61 ± 12.96 1.312 0.192 >0.57 58.92 ± 13.45 Alcohol ≤0.16 56.34 ± 12.30 0.621 0.536 >0.17 57.90 ± 14.27 Drugs ≤0.21 55.30 ± 11.85 1.541 0.126 >0.22 59.16 ± 14.51 Legal 0 58.41 ± 14.57 0.528 0.599 >0.1 56.74 ± 12.93 Socio-familiar ≤0.36 54.45 ± 13.15 2.333 <0.021* >0.37 60.24 ± 12.73 Psychological ≤0.43 51.18 ± 10.71 5.289 <0.001*,** >0.44 63.07 ± 12.90 † The sample was dichotomized by using median. Therefore, the percentage in each group is 50%. * The result is statistically significant. ** The result is statistically significant after Bonferroni correction. alexithymia levels act impulsively as a response to distressed levels of alexithymia in patients with SUD, and, in previous moods (53). Similarly, the relationship between impulsivity and studies, PCS has been related to difficulties with identifying alexithymia has been described in patients with cannabis use feelings (36). disorder and pathological gambling (18, 54). Finally, although substance-induced psychosis was only Regarding the above, Thorberg et al. (38) state that loss significantly related to higher levels of alexithymia in the bivariate of control over drinking could mediate between alexithymia analysis, we consider it is important to analyze this correlation and HRQoL (38). This point is important because we have since, as far as we know, this is the first time it is reported. found a negative relationship between HRQoL and alexithymia This finding could be related to studies in other populations, scores. This relationship between HRQoL impairments and which state that alexithymia may be a risk factor for psychotic alexithymia in SUD patients has previously been described experiences (28, 34). Thus, it can be hypothesized that, in (36, 38), and it could be analyzed in several ways. In the the current case, substance use led to psychotic experiences in current research, SUD patients with higher levels of alexithymia patients with higher levels of alexithymia. Also, several points also exhibited more psychiatric comorbidities, and it has frequently considered to be risk factors for substance-induced been stated that HRQoL perceptions could vary depending psychosis were present in patients with higher alexithymia levels, on the presence of psychiatric comorbidities (2). Evren et al. such as cannabis use disorder (35). Future studies should further (36) also explain that difficulties in identifying feelings are analyze this result, discriminating between the various substances connected to HRQoL, and such difficulties could influence how used, as some substances induce psychosis more frequently than patients perceive their HRQoL (36). Additionally, negative affects others (35). (anxiety and depression) correlate with worse PCS in HRQoL Despite its intriguing and novel results, this study does present among SUD patients (2). Interestingly, in this research, after some limitations. This research had a cross-sectional design, and, multivariate analysis, PCS was significantly connected to higher therefore, the findings should be examined in longitudinal studies Frontiers in Psychiatry | www.frontiersin.org 5 April 2021 | Volume 12 | Article 659063 Palma-Álvarez et al. Alexithymia in Substance Use Disorders TABLE 3 | Current psychiatric comorbidity and psychological symptoms of patients, analyzed by alexithymia levels. Variable Total % Mean score of TAS-20 ± SD t p Psychiatric disorders† Dual diagnosis Yes 63.7 60.14 ± 11.45 2.510 <0.017* No 36.3 53.92 ± 12.85 Mood spectrum disorders Yes 41.7 61.18 ± 13.25 2.356 <0.021* No 58.3 55.41 ± 11.46 Anxiety spectrum disorders Yes 27.3 60.53 ± 9.83 1.48 0.137 No 72.7 56.46 ± 13.60 Psychotic spectrum disorders Yes 21.1 62.96 ± 12.99 2.215 <0.034* No 78.9 56.30 ± 12.06 Primary psychotic disorders Yes 13.9 60.53 ± 12.91 0.906 0.367 No 86.1 57.38 ± 12.46 Induced psychosis Yes 11.1 68.67 ± 11.18 3.457 <0.004*,** No 88.9 56.71 ± 12.24 Attention deficit hyperactivity disorder Yes 8.4 62.13 ± 8.27 1.154 0.252 No 91.6 57.08 ± 12.08 Personality disorders† Any personality disorder Yes 31.3 59.39 ± 13.91 1.126 0.263 No 68.7 56.37 ± 11.62 Cluster A personality disorders Yes 4.0 64.50 ± 18.43 1.159 0.249 No 96.0 57.17 ± 12.16 Cluster B personality disorders Yes 27.3 59.56 ± 14.33 1.104 0.272 No 73.7 56.47 ± 11.58 - Antisocial personality disorder Yes 20.0 63.15 ± 14.15 2.080 <0.048* No 80.0 56.04 ± 11.61 - Borderline personality disorder Yes 10.1 62.00 ± 14.60 1.265 0.209 No 89.9 56.79 ± 12.10 - Narcissistic personality disorder Yes 4.0 47.75 ± 9.81 1.609 0.111 No 96.0 57.86 ± 12.39 Cluster C personality disorder Yes 4.0 60.50 ± 7.42 0.498 0.620 No 96 57.33 ± 12.59 Psychological traits/symptoms BDI-I ≤18 52.7 51.94 ± 11.01 5.396 <0.001*,** >19 47.3 64.66 ± 12.18 State anxiety (STAI)‡ ≤28 52.87 ± 11.87 3.970 <0.001*,** >29 62.95 ± 11.93 Trait anxiety (STAI)‡ ≤33 51.82 ± 11.39 4.848 <0.001*,**,*** >34 63.51 ± 12.13 BIS-11 total score‡ ≤62 52.96 ± 11.89 3.957 <0.001*,**,*** >62 62.91 ± 12.33 Functional impulsivity (DII)‡ ≤32 56.48 ± 11.84 0.222 0.825 >33 57.11 ± 15.03 Dysfunctional impulsivity (DII)‡ ≤36 53.45 ± 12.07 2.691 <0.009*,** >37 60.59 ± 13.38 HRQoL (SF-36) Physical component summary HRQoL ≤50 64.6 60.52 ± 11.59 4.189 <0.001*,**,*** >51 35.4 50.29 ± 11.35 Mental component summary HRQoL ≤50 79.2 59.11 ± 11.86 3.539 <0.001*,** >51 20.8 49.10 ± 11.08 † Other disorders were not analyzed due to small sample size (<5 patients per group). ‡ The sample was dichotomized by using median. Therefore, the percentage in each group is 50%. BDI-I, Beck Depression Inventory; BIS-11, Barratt Impulsivity Scale; DII, The Dickman Impulsivity Inventory; HRQoL, Health-related Quality of Life measured by the The Short-Form 36; STAI, Stait-Trait Anxiety Inventory. * The result is statistically significant. ** The result is statistically significant after Bonferroni correction. *** The result is statistically significant after multivariate analysis. Frontiers in Psychiatry | www.frontiersin.org 6 April 2021 | Volume 12 | Article 659063 Palma-Álvarez et al. Alexithymia in Substance Use Disorders to evaluate their bilateral association and relevance. Regarding for distribution to others than the research group that conducted the TAS-20, some authors argue that, as it is a self-rated scale, the study as may violate ethical and/or legal regulations of its results could be biased (9, 16). However, it is still considered written consent. the gold standard instrument for evaluating alexithymia (9). We did not individually analyze the three TAS-20 subfactors, ETHICS STATEMENT but such a sub-analysis could generate deeper conclusions. Additionally, we used SCID-I and SCID-II for comorbidity The studies involving human participants were reviewed and assessment. Despite SCID-I and SCID-II have demonstrated approved by the local Hospital Ethics Committee according to their reliability and have hugely been used (and are still in the World Medical Association’s Declaration of Helsinki. The use) in modern research, those interviews use DSM-IV criteria sampled patients provided their written informed consent to (55). Hence, the current findings should be analyzed taking participate in this study. into account that some points are not comparable to the new version of DSM. On the other hand, this research has provided AUTHOR CONTRIBUTIONS new insights concerning alexithymia in SUD. The study was conducted in a clinical setting, and, hence, it presents information RP-Á, LG-L, and CR contributed to the design and coordination for routine clinical practice in addiction treatment centers. To the of the study. RP-Á, ER-C, NM-L, AS-M, and PS-P collected the extent of our knowledge, some of the analysis presented here has sample. CD, MP-O, AS-M, and PS-P performed psychological never been conducted before (especially among Spanish patients evaluation. RP-Á, CD, LG-L, and JR-Q prepared the data with SUD). and performed data analyses. RP-Á, ER-C, MR-M, and JR-Q According to the results described above, we conclude performed the literature review. RP-Á, ER-C, MP-O, MR-M, that, in SUD patients, higher alexithymia levels are related to and CR wrote the initial version of this manuscript. All authors psychiatric comorbidities (especially mood spectrum disorders participated in the interpretation of the data, edition, reading, and substance-induced psychosis), increased levels of depression, and approved the last version of this manuscript. anxiety, and impulsivity, and worse HRQoL. Trait anxiety, impulsivity, and PCS are the most important factors associated ACKNOWLEDGMENTS with higher levels of alexithymia in SUD patients. Thus, it is important to evaluate these factors in clinical practice and The authors wish to thank to the nurse team of the outpatient provide accurate treatment programs including them. center for SUD treatment of Hospital Universitari Vall d’Hebron (especially to Ms. Laura Camañes, Mr. Miguel Cantillo, Mr. DATA AVAILABILITY STATEMENT Eduardo Castrillo, and Mr. Manuel Peláez) for their support in the recruitment. 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(2020) 46:505–16. doi: 10.1093/schbul/sbz102 (2018). doi: 10.1007/978-3-319-57111-9_2011 Frontiers in Psychiatry | www.frontiersin.org 8 April 2021 | Volume 12 | Article 659063 Palma-Álvarez et al. Alexithymia in Substance Use Disorders Conflict of Interest: RP-Á has received fees to give talks for Exeltis, Lundbeck, Reckitt-Benckiser/Indivior. He received a medical education grant for Gilead. MSD, Mundipharma and Takeda. ER-C has received fees to give talks for LG-L has received fees to give talks for Janssen-Cilag, Lundbeck, Servier, Otsuka, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Lilly, Servier, Rovi, Juste. She has and Pfizer. received financial compensation for projects with Lundbeck, Esteve, Pfizer, Rovi, Exeltis, Servier, and Eisai. She has received financial compensation for her The remaining authors declare that the research was conducted in the absence of participation as a board member of Janssen-Cilag. She has no other relevant any commercial or financial relationships that could be construed as a potential affiliations or financial involvement with any organization or entity with a conflict of interest. financial interest in or financial conflict. NM-L has received fees to give talks for Janssen-Cilag, Lundbeck and Servier. JR-Q has received fees as speaker Copyright © 2021 Palma-Álvarez, Ros-Cucurull, Daigre, Perea-Ortueta, Serrano- from Janssen-Cilag, Shire, Lilly, Ferrer, Medice and Rubió. He has received Pérez, Martínez-Luna, Salas-Martínez, Robles-Martínez, Ramos-Quiroga, Roncero research funding from Janssen-Cilag, Lilly, Ferrer, Lundbeck and Rubió. CR and Grau-López. This is an open-access article distributed under the terms of has received fees to give lectures for Janssen-Cilag, Ferrer-Brainfarma, Pfizer, the Creative Commons Attribution License (CC BY). The use, distribution or Indivior, Lundbeck, Otsuka, Servier, GSK, Rovi, Astra, Gilead, MSD, Sanofi and reproduction in other forums is permitted, provided the original author(s) and the Exeltis. He has received financial compensation for his participation as a board copyright owner(s) are credited and that the original publication in this journal member of JanssenCilag, Lundbeck, Gilead, MSD, Indivior and Mundipharma. is cited, in accordance with accepted academic practice. No use, distribution or He has carried out the PROTEUS project, which was funded by a grant from reproduction is permitted which does not comply with these terms. Frontiers in Psychiatry | www.frontiersin.org 9 April 2021 | Volume 12 | Article 659063