ORIGINAL RESEARCH published: 22 July 2021 doi: 10.3389/fpsyt.2021.701140 Cognition in Recent Suicide Attempts: Altered Executive Function Jessica Fernández-Sevillano 1,2,3 , Susana Alberich 2,3 , Iñaki Zorrilla 1,2,3 , Itxaso González-Ortega 2,3 , María Purificación López 1,2,3 , Víctor Pérez 3,4 , Eduard Vieta 3,5 , Ana González-Pinto 1,2,3*† and Pilar Saíz 3,6† 1 Department of Neuroscience, Universidad del País Vasco/Euskal Herriko Unibertsitatea, Bilbao, Spain, 2 Department of Psychiatry, Bioaraba Research Institute, Araba University Hospital, Vitoria-Gasteiz, Spain, 3 Biomedical Research Networking Centre in Mental Health (CIBERSAM), Madrid, Spain, 4 Institut Hospital del Mar d’Investigacions Mèdiques (IMIM) Department of Psychiatry, Institut de Neuropsiquiatria i Addicions, Hospital del Mar, Universidad Autónoma de Barcelona, Barcelona, Spain, 5 Hospital Clinic, Institute of Neuroscience, University of Barcelona, Institut D’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, 6 Department of Psychiatry, Universidad de Oviedo, Instituto de Investigación Sanitaria del Principado de Asturias, Servicio de Salud del Principado de Asturias, Oviedo, Spain Background: Neuropsychological alterations can lead to inaccurate perception, interpretation, and response to environmental information, which could be a risk factor for suicide. Methods: Ninety-six subjects were recruited from the Psychiatry Department of the Araba University Hospital—Santiago, including 20 patients with a recent attempt and Edited by: Javier Ortuño Sierra, diagnosis of major depressive disorder (MDD) according to DSM-V, 33 MDD patients with University of La Rioja, Spain history of attempted suicide, 23 non-attempter MDD patients, and 20 healthy controls. Reviewed by: All participants underwent a clinical interview and neuropsychological assessment on Adriana Díez-Gómez, the following cognitive domains: working memory, processing speed, decision-making, University of La Rioja, Spain Ana Ciarreta, executive function, and attention. Backward multiple regressions were performed University of La Rioja, Spain adjusting for significant confounding variables. For group comparisons, ANOVA and *Correspondence: Bonferroni post-hoc tests were performed with a p < 0.05 significance level. Ana González-Pinto anamaria.gonzalez-pintoarrillaga@ Results: The patient groups did not differ regarding severity of depression and stressful osakidetza.eus events in the last 6 months. In comparison to healthy controls, depressed patients † Theseauthor contributed equally and with lifetime suicide attempts had more general trauma (p = 0.003), emotional abuse share last and senior authorship (p = 0.003), emotional negligence (p = 0.006), and physical negligence (p = 0.009), and depressed patients with recent suicide attempts had experienced more child Specialty section: This article was submitted to sexual abuse (p = 0.038). Regarding neuropsychological assessment, all patient Psychopathology, groups performed significantly worse than did healthy controls in processing speed, a section of the journal Frontiers in Psychiatry decision-making, and attention. Comparisons between patient groups indicated that Received: 27 April 2021 recent suicide attempters had poorer performance on executive function in comparison Accepted: 01 June 2021 to both depressed lifetime attempters and depressed non-attempters (B = 0.296, Published: 22 July 2021 p = 0.019, and B = 0.301, p = 0.028, respectively). Besides, women with recent Citation: attempts had slightly better scores on executive function than males. Regarding the rest Fernández-Sevillano J, Alberich S, Zorrilla I, González-Ortega I, of the cognitive domains, there were no significant differences between groups. López MP, Pérez V, Vieta E, González-Pinto A and Saíz P (2021) Conclusion: Executive function performance is altered in recent suicide attempts. As Cognition in Recent Suicide Attempts: impaired executive function can be risk factor for suicide, preventive interventions on Altered Executive Function. suicide should focus on its assessment and rehabilitation. Front. Psychiatry 12:701140. doi: 10.3389/fpsyt.2021.701140 Keywords: suicide, major depressive disorders, cognition, executive function, trauma Frontiers in Psychiatry | www.frontiersin.org 1 July 2021 | Volume 12 | Article 701140 Fernández-Sevillano et al. Cognition in Suicide INTRODUCTION (≤30 days), 33 patients with a past suicide attempt during their lifetime and hospitalized for MDD episodes, 23 without history Suicide is a major health issue worldwide involving nearly of suicidal attempts and hospitalized for MDD episodes, and 20 800,000 deaths per year (1). Identifying risk factors can lead healthy controls with no personal or family history of mental to a better understanding and prevention of this behavior (2). illness matched by age and sex with a reference group, that is, Age, sex, history of previous attempts, genetic predisposition, a recent suicide attempt group. Suicide attempt was defined as drug consumption, and early adversity, among others, have been a “self-initiated sequence of behaviors by an individual who, at extensively reported as relevant features that can predict a suicide the time of the initiation, expected that the set of actions would attempt (3–6). lead to his or her own death” (DSM-5). The exclusion criteria for Additionally, neuropsychological performance has been the three groups including patients were: presence of psychotic linked to suicide in several studies across all the life span. symptoms and other comorbid psychiatric disorders with the Impaired complex cognition, social cognition, and episodic exception of tobacco use disorder, acute infections, neurological memory (7, 8) were reported in adolescents at risk of illness, intellectual disability, dementia, organic diseases that suicide. In children with a family history of suicide attempts, compromise cognitive functioning, and cognitive syndromes. cognitive, attention, and language reasoning have been described, In addition to this, the exclusion criteria for healthy controls increasing their risk of reproducing a suicide attempt themselves included either personal or a family history of major psychiatric (9). In contrast, McHugh et al. (10) found better cognitive disorders. All participants were between 18 and 65 years old functioning on processing speed, verbal learning, working and had signed an informed consent. This study was approved memory, delayed memory, and verbal fluency in suicidal by the ethical board of the Araba University Hospital and was youngsters and young adults. conducted according to the Declaration of Helsinki (25). In adult and elderly populations, many studies have provided evidence of alterations in executive function (11–13), attention (14), memory (15), and decision-making (13, 16, 17) in Procedure and Measures suicide attempters. Deficits in these cognitive domains, especially After recruitment and signature of the informed consent, executive function that organizes and directs behavior, can lead to each participant had an interview with a psychologist for an inaccurate perception, interpretation, retrieval, and response sociodemographic data collection and clinical assessment of to environmental information, which may result in an inflexible, depressive symptoms, stressful events, and childhood trauma. pessimistic way of thinking about their future and themselves Depressive symptom severity was assessed using the 17-item (18). Thus, these cognitive deficits may imply a higher risk of Spanish version of the Hamilton Depression Rating Scale suicide as a response to adverse life events. In summary, existing (HDRS) (26, 27), a structured instrument widely used in the evidence supports a connection between cognition and suicide. psychiatric field (28–30) that offers a quantitative measure of However, these studies do not determine the specific cognitive the severity of depressive symptoms in a clinical population alterations involved in a recent suicide attempt, that is, the according to the criteria of the evaluator who conducts the current altered processes that surround and may contribute to clinical interview. Each item has between three and five possible suicidal behavior. Besides, these cognitive alterations are not responses with 0–2 or 0–4 scores, respectively, and the total unique to suicide and have also been described in depressive score ranges from 0 to 52. The 17-item Spanish version has patients (19–24); therefore, it remains unclear which specific good reliability, with a Cronbach’s α of 0.72, and validity cognitive domains are altered in recent suicidal behavior. with a correlation with other scales for depressive symptoms Considering data scarcity, the aim of this study was to explore (Montgomery–Asberg and Beck’s Depression Inventory) ranging cognitive alterations in recent suicide attempts. For this purpose, from 0.8 to 0.9. Recent (6 months) stressful events were measured we compared the neuropsychological performance of depressed patients with a recent attempt, depressed patients with a history of suicide, depressed non-attempters, and healthy controls on TABLE 1 | Cognitive domains. the following cognitive domains: working memory, processing Working WAIS-IV Arithmetic: total score speed, decision-making, executive function, and attention. memory WAIS-IV Digit: total score Wechsler (45) MATERIALS AND METHODS Processing WAIS-IV Symbol Search: total score speed WAIS-IV Coding: total score Participants Wechsler (45) Ninety-six participants were recruited from the Psychiatry Department of the Araba University Hospital—Santiago. All Decision- Iowa gambling test: total money score Bechara et al. (46) patients were diagnosed of major depressive disorder (MDD) making according to the Diagnostic and Statistical Manual of Mental Executive Wisconsin sorting card test: categories, errors, function perseverative errors Heaton (47) Disorders, 5th edition (DSM-5) criteria and were receiving Stroop test: interference score Golden (48) psychopharmacological treatment for their condition. The FAS test: total correct answers Buriel et al. (49) sample was categorized into the following groups: 20 depressed patients who were hospitalized after a recent suicide attempt Attention Stroop test: color word Golden (48) Frontiers in Psychiatry | www.frontiersin.org 2 July 2021 | Volume 12 | Article 701140 Fernández-Sevillano et al. Cognition in Suicide using the Spanish version of the List of Threatening Experiences Comparisons between groups regarding the sociodemographic (LTE) (31, 32), a 12-item brief questionnaire with yes/no and clinical variables were performed with ANOVA followed responses regarding personal, relational, financial, and health by Bonferroni post-hoc testing for continuous variables and chi- problems. This questionnaire has a high test–retest reliability square for categorical variables. For the analyses of cognitive (κ = 0.61–0.87) and is a valid and reliable measure of stressful performance, measures selected from each test (Table 1) were events in mental health, specifically in depression (OR = 1.64– gathered into the corresponding cognitive domain that is 2.57) (32), which has been previously used in studies with evaluated and the obtained scores were transformed to average z- psychiatric populations (33–36). Childhood abuse and neglect scores. Backward multiple regressions were performed adjusting were assessed with the Spanish version of the Childhood Trauma for the following confounding variables: age, sex, economic Questionnaire—Short Form (CTQ-SF) (37), a self-administered status, education, marital status, drug consumption (tobacco, 28-item questionnaire with five Likert responses (never, rarely, cannabis, and alcohol), and severity of depressive symptoms sometimes, often, and always) that has been extensively used (38– according to the HDRS. In each model, only significant 43) to evaluate the maltreatment dimensions that were detected confounders were taken into account. in the original factorial analysis for construct validity (44): emotional (Cronbach’s α = 0.87), physical (Cronbach’s α = 0.89) and sexual abuse (Cronbach’s α = 0.94) and physical (Cronbach’s RESULTS α = 0.66) and emotional (Cronbach’s α = 0.83) neglect (37). Besides, the participants underwent a neuropsychological Sociodemographic and Clinical Variables assessment using a standardized test on the following cognitive There were no significant differences between groups regarding domains: working memory, processing speed, decision-making, sociodemographic variables (Table 2). In the recent attempt executive function, and attention. The test and measures used group, 35% of patients were recruited after an index attempt, in each domain (Table 1) were adapted from previous existing 40% of patients reattempted for the second time, and 60% of literature on cognitive assessment in mental disorders (50, 51). patients had more than two reattempts. In the lifetime attempt group, 6.3% of patients had attempted suicide once, 34.4% twice, Statistical Analyses and 59.3% more than twice. Regarding psychiatric medication, Statistical analysis was performed by an expert biomedical the majority had similar treatments as 94% were under statistician. Data were checked for Gaussian distribution. polytherapy consisting of antidepressants and benzodiazepines, TABLE 2 | Demographic and clinical variables. Recent Lifetime Depressed Healthy Statistical attempters attempters non-attempters controls contrast (n = 20) (n = 33) (n = 23) (n = 20) (p) Sex, n (%) Female 13 (65%) 26 (78.8%) 18 (78.3%) 14 (70%) X 2 = 1.617; p = 0.656 Male 7 (35%) 7 (21.2%) 5 (21.7%) 6 (30%) Age, mean (SD) 44.70 (8.785) 44.45 (12.765) 50.57 (9.926) 44.58 (9.221) F (3,91) = 1.842; p = 0.145 Education level, n (%) Primary 2 (10%) 6 (18.2%) 5 (21.7%) 0 (0%) X 2 = 9.886; p = 0.360 Secondary 7 (35%) 11 (33.3%) 7 (30.4%) 6 (30%) Preparatory 5 (25%) 9 (27.3%) 6 (26.1%) 4 (20%) University 6 (30%) 7 (21.2%) 5 (21.7%) 10 (50%) Economic status, n (%) Low 7 (38.9%) 10 (37%) 10 (50%) 6 (33.3%) X 2 = 5.611; p = 0.468 Medium 9 (50%) 11 (40.7%) 10 (50%) 9 (50%) High 2 (11.1%) 6 (22.3%) 0 3 (16.7%) Previous suicide attempts, mean (SD) 1.47 (1.87) 2.34 (2.04) – – t = −1.52; p = 0.1 Age of index attempt, mean (SD) 33.55 (11.91) 31.83 (15.35) – – t = 0.42; p = 0.67 Previous depressive episodes, mean (SD) 2.60 (2.90) 7.50 (9.81) 2.38 (1.59) – F (2,47) = 2.16; p > 0.05 Depression severity (HDRS), mean (SD) 15.50 (7.23) 17.87 (6.54) 14.36 (8.93) 1.60 (2.09) F (3,89) = 25.741; p < 0.01 Stressful events (LTE), mean (SD) 2.80 (1.70) 2.53 (2.11) 2.56 (1.90) 0.5 (1.15) F (3,91) = 7,281; p < 0.01 CTQ total, mean (SD) 57 (25.63) 64.1 (21.66) 52.57 (23.06) 38.15 (7.12) F (3,80) = 4.54; p < 0.05 CTQ emotional abuse, mean (SD) 11.15 (6.63) 13.19 (6.16) 10.38 (6.08) 7.57 (2.90) F (3,82) = 3.112; p < 0.05 CTQ physical abuse, mean (SD) 8.80 (4.93) 8.13 (5.02) 8.10 (5.73) 6.21 (2.36) F (3,82) = 0.813; p = 0.49 CTQ sexual abuse, mean (SD) 10 (7.48) 8.81 (5.58) 6.14 (2.15) 5.07 (0.27) F (3,82) = 3.789; p < 0.05 CTQ emotional negligence, mean (SD) 10.2 (5.02) 14.13 (6.07) 10.67 (5.94) 8.08 (1.85) F (3,80) = 4.736; p < 0.05 CTQ physical negligence, mean (SD) 11.55 (2.58) 13.06 (3.18) 11.68 (3.48) 9.93 (1.90) F (3,83) = 3.770; p < 0.05 HDRS, Hamilton Depression Rating Scale; LTE, List of Threatening Experiences; CTQ, Childhood Trauma Questionnaire. Frontiers in Psychiatry | www.frontiersin.org 3 July 2021 | Volume 12 | Article 701140 Fernández-Sevillano et al. Cognition in Suicide whereas 6% of patients were under monotherapy of either of group for adjusted regressions was afterwards changed to those treatments. recent attempters. The results yielded significant differences on In addition to having similar medication profiles, the severity the executive function domain. Both lifetime attempters and of depressive symptoms was equally distributed across groups. depressed non-attempters had significantly higher scores in Bonferroni post-hoc analyses revealed that all groups had this domain in comparison to recent attempters (B = 0.296, significantly higher scores for depressive symptoms measured p = 0.019, and B = 0.301, p = 0.028, respectively); that is, by the HDRS than did the healthy controls (p < 0.01 in each recent suicide attempters had poorer performance on executive comparison), but the severity of depression was similar across function. However, there were no significant differences between patient groups. Besides, healthy controls had fewer stressful groups in the rest of the cognitive domains. events in the last 6 months than each of the patient groups (p Further analyses showed that there was an interaction < 0.05 in each comparison). between group (depressed recent attempters, depressed lifetime Also, post-hoc analyses of the CTQ-SF scores indicate greater attempters, and depressed non-attempters) and sex on executive general trauma (p = 0.003), emotional abuse (p = 0.003), performance (Table 5). According to these results, women with emotional negligence (p = 0.006), and physical negligence (p recent attempts had slightly better scores on executive function = 0.009) in patients with a history of suicide attempts in than did males. However, in the rest of the groups, men comparison to healthy controls. Besides, patients with recent outperformed women, especially in depressed non-attempter suicide attempts reported higher scores of child sexual abuse patients, with a large effect size indicating a strong interaction (p = 0.038) than did healthy controls. between sex and group. Performance on Cognition DISCUSSION The scores on the five domains included in this study are presented in Table 3. The main finding of this study is that MDD patients with Backward stepwise multiple regressions were performed suicide attempts in the last 30 days have significantly poorer and adjusted by significant confounders (age, sex, economic performance on executive function compared to MDD patients level, marital status, years of education, severity of depression, with a previous history of suicide attempts and to MDD non- and substance consumption) with healthy controls as the attempter patients. This finding indicates that suicide might reference group. Healthy controls performed significantly better be accompanied with an altered performance on executive in processing speed, decision-making, and attention than did function. Deficits in this cognitive domain have already been all groups of depressed patients, with no differences between described in patients with a history of suicidality (12, 14, 52– them (Table 4). 56) and in depressed patients without suicidal behavior (23, As the main objective of this study was to determine 53), especially in those with poor treatment response (57), the cognitive differences between recent suicide attempters but to the best of our knowledge, this is the first study that and current non-suicidal depressed patients, the reference compares MDD patients with recent attempts, MDD patients TABLE 3 | Cognitive domains by groupa . Recent attempters Lifetime attempters Depressed non-attempters Healthy controls (n = 20) (n = 33) (n = 23) (n = 20) Working memory −0.577 (0.822) −0.825 (0.867) −0.798 (0.845) 0 (0.784) Processing speed −1.002 (0.821) −1.403 (1.444) −1.306 (1.411) 0 (0.944) Decision making −0.772 (1.089) −0.726 (1.053) −0.873 (0.889) 0 (1.000) Executive function −0.191 (0.256) 0.066 (0.484) 0.070 (0.530) 0.021 (0.313) Attention −0.910 (0.770) −1.025 (0.667) −0.913 (0.646) 0.046 (0.781) a Data are presented as means and standard deviations. All values are z-scores. TABLE 4 | Multiple regressiona . Working memory Processing Decision-making Executive Attention speed function Recent attempters −0.113 −1.065* −0.829* −0.229 −0.604* Lifetime −0.221 −1.416** −0.664* 0.068 −0.577* attempters Depressed −0.313 −1.050* −0.782* 0.072 −0.567* non-attempters *p < 0.05; **p < 0.001. a Data are presented as adjusted B coefficients assuming “healthy controls” as the reference group. Frontiers in Psychiatry | www.frontiersin.org 4 July 2021 | Volume 12 | Article 701140 Fernández-Sevillano et al. Cognition in Suicide TABLE 5 | Effect sizes of being female on executive functiona . disorder is consistent with previous literature (21, 54, 72, 73). According to our findings, these alterations are different from Femaleb those associated specifically with recent suicide attempts and, Recent attempters 0.088 (−0.301, 0.478) therefore, different cognitive processes are specifically more Lifetime attempters −0.239 (−0.624, 0.146) altered in each condition. Depressed non-attempters −0.663 (−1.134, −0.192) Apart from the neurocognitive deficits, traumatic life events Healthy controls −0.189 (−2.058, 1.680) are also associated with a higher risk of suicide. Patients with a history of childhood maltreatment (74–76) and sexual abuse a Adjusted b Effect for potential confounders. (77) have an increased risk of suicidal behavior in their adult size is interpreted as the difference in average executive function domain between females and males. life. In our sample, patients with recent suicide attempts reported more child sexual abuse than the rest of the groups. Patients with a history of suicide reported more general trauma, emotional abuse, and negligence, and in general, patients had more recent with lifetime attempts, MDD non-attempter patients, and stressful events than did the controls. Furthermore, the link healthy controls. between trauma, executive function alterations, and suicidal Executive function directs thought and behavior toward an behavior has also been described by several authors. In a recent objective in order to respond to current or future situational study by Zelazny et al. (76), higher scores on executive function demands. According to the comprehensive model proposed by were protective against suicide in individuals with childhood Miyake et al. (58), this implies the inhibition of responses, maltreatment. Carvalho et al. (78) found that maltreated children shifting between tasks and the constant update of the working performed worse than did non-maltreated children in executive memory. Other authors also include planning, decision-making, function tests, and according to the study by Dannehl et al. working memory, and error detection among its functions (79), these differences are also present in adults with a history (59, 60). All in all, these processes allow the deliberate and of childhood adversity, especially in those with physical abuse intentional goal-directed response to environmental stimuli and neglect. and are subject to the influence of individual factors, such In conclusion, recent suicidal behavior is specifically as emotional regulation, personality traits, and even traumatic associated with deficits on executive function, which suggests a events (61–63). Deficits in these processes can lead to the cognitive dysfunction on information processing and response, dysregulation of emotion, thoughts, and actions (64), which especially in critical events. As executive function can be trained might contribute to considering suicide as a solution under and improved (80), cognitive screening and stimulation may be critical circumstances (15). In addition, these alterations may proposed as a strategy for suicide prevention in at-risk patients. also increase interpersonal difficulties, increasing the risk of Future studies are needed to identify possible differences between attempted suicide (17). sex in each cognitive domain for a more personalized approach According to our results, sex has an influence on executive and for a better understanding of early detection vulnerability function. The slightly better performance of women in the recent factors that may enable us to prevent suicide in at-risk patients. attempt group may be possibly explained by the fact that higher impulsivity scores have been related to men (61), which implies a Limitations tendency to think and behave with less planning, error detection, This study has a number of limitations. Recent and past trauma cognitive flexibility, and inhibitory control (65), processes that events were assessed using self-administered and self-reported are under control of the executive function. Therefore, men are scales in MDD patients who can be biased when reporting this more likely to make non-adaptive choices under demanding or information. As more women have recently attempted suicide stressing circumstances as risky behavior or suicide. However, than men, the sex-related differences on executive function depressed non-attempter men had significantly better executive found in recent attempters must be interpreted with caution, function performance. This may be due to the fact that women and further confirmatory studies are advisable. Moreover, some have more severe cognitive symptoms of depression, such as factors that have been described in the literature as potentially rumination and hypochondria (66), and a greater impact on influencing suicidal behavior in major depression, such as anxiety their functionality (67). Apart from psychological factors, there (81) or mixed symptoms (82), were not assessed. are also biological differences, such as sex hormones (68, 69), dysregulation of the hypothalamus–pituitary–adrenal (HPA) axis (70), and inflammatory parameters (71), that make depression DATA AVAILABILITY STATEMENT more adverse for women. The raw data supporting the conclusions of this article will be Additionally, the neuropsychological assessment results made available under request to the authors. revealed that all depressed patients with similar depression severity performed significantly worse than did healthy controls in processing speed, decision-making, and attention, but with ETHICS STATEMENT no difference between groups. This suggests that depressed patients have alterations in these specific dimensions associated The studies involving human participants were reviewed with their psychopathological process; that is, major depressive and approved by CEIC EUSKADI. The patients/participants Frontiers in Psychiatry | www.frontiersin.org 5 July 2021 | Volume 12 | Article 701140 Fernández-Sevillano et al. Cognition in Suicide provided their written informed consent to participate in Development Fund (ERDF)/European Social Fund Investing this study. in your future, and the Government of the Principality of Asturias PCTI-2018-2022 IDI/2018/235). Foundation for Health Innovation and Research (BIOEF); Networking Center AUTHOR CONTRIBUTIONS for Biomedical Research in Mental Health (CIBERSAM), the Basque Government (Grant No: 2017111104); and the JF-S drafted and wrote the manuscript. SA performed statistical University of the Basque Country (Grant No: 321218ELCY). analyses and contributed to data interpretation. IZ, ML, VP, and The Psychiatric Research Department in Araba University EV revised the manuscript for important intellectual content Hospital is supported by the Stanley Research Foundation and provided scientific advice. IG-O provided funding sources (Grant No: 03-RC-003). JF-S was a beneficiary of the Pre- and scientific advice. PS and AG-P designed the study, corrected PhD Training Programme of the Basque Government. No the manuscript, gave final approval of the version to be funding source in this study was involved in the study published, and ensured the scientific accuracy and integrity design, collection, analysis and interpretation of data, in the of the work. AG-P and PS should be considered joint senior writing of the report, or in the decision to submit the paper authors. All authors contributed to the article and approved the for publication. submitted version. ACKNOWLEDGMENTS FUNDING We want to acknowledge the Center for Biomedical Research This work was supported by Carlos III Health Research in Mental Health (CIBERSAM), Carlos III Health Research Institute [Grant Numbers PI15/00789, PI17/01433, PI18/01055, Institute, the Basque Government, the University of the Basque and PI19/00569 (co-financed by the European Regional Country (UPV/EHU), and Bioaraba Research Institute. REFERENCES 11. 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Jiménez-Treviño L, Saiz PA, García-Portilla MP, Blasco-Fontecilla H, Carli V, Copyright © 2021 Fernández-Sevillano, Alberich, Zorrilla, González-Ortega, López, Iosue M, et al. 5-HTTLPR-brain-derived neurotrophic factor (BDNF) gene Pérez, Vieta, González-Pinto and Saíz. This is an open-access article distributed interactions and early adverse life events effect on impulsivity in suicide under the terms of the Creative Commons Attribution License (CC BY). The use, attempters. World J Biol Psychiatry Off J World Fed Soc Biol Psychiatry. (2019) distribution or reproduction in other forums is permitted, provided the original 20:137–49. doi: 10.1080/15622975.2017.1376112 author(s) and the copyright owner(s) are credited and that the original publication 76. Zelazny J, Melhem N, Porta G, Biernesser C, Keilp JG, Mann JJ, et in this journal is cited, in accordance with accepted academic practice. No use, al. Childhood maltreatment, neuropsychological function and suicidal distribution or reproduction is permitted which does not comply with these terms. Frontiers in Psychiatry | www.frontiersin.org 8 July 2021 | Volume 12 | Article 701140