Emotional memory bias in binge drinking women

1 EMOTIONAL MEMORY BIAS IN BINGE DRINKING FEMALES: REMEMBERING THE HALF EMPTY GLASS Carbia, C1; Corral, M2; Caamaño-Isorna, F3; Cadaveira, F2 1 APC Microbiome Ireland, Biosciences Building, University College Cork, Cork, Ireland 2 Department of Clinical Psychology and Psychobiology, University of Santiago de Compostela, Galicia, Spain 3 Consortium for Biomedical Research in Epidemiology & Public Health (CIBERESP). Department of Preventive Medicine, University of Santiago de Compostela, Galicia, Spain 2 Corresponding author: Montserrat Corral, Department of Clinical Psychology and Psychobiology, University of Santiago de Compostela, 15782, A Coruña, Galicia, Spain Email: [email protected] 3 Abstract Background: Heightened emotionality and overrepresentation of memories are typical features of adolescence. Binge drinking (BD) during emerging adulthood has been linked to cognitive difficulties such as deficits in episodic memory. Despite that impairments in emotional functioning have been associated with the development of alcohol use disorders, particularly in females, the emotional sphere has been relatively unexplored in BDs. Therefore, the purpose of this study is to examine the effects of BD in emotional episodic memory from a gender perspective. Methods: One hundred and eighty (96 females) university students were followed during two years (18-20 years old) and their alcohol use was recorded. In the last assessment, participants completed an emotional list-learning task. Generalized linear mixed models were applied separately for males and females, in accordance with sex differences in the development of emotion circuitry. Results: In females, BD was associated with an emotional memory bias in favor of negative information and lower recall of positive and neutral words. In addition, females BDs showed more false alarms to negative distractors. Whereas in males, no alcohol-related effects were found. Conclusions: Female BDs present a negative memory bias and poor learning and delayed episodic recall linked to the interference of negative content, which suggests difficulties in disengaging attention to salient negative stimuli and a reduction of inhibitory capacities. This might result in greater vulnerability to alcohol-related emotional disturbances among women. Further research is needed to understand the role of emotional regulation in the escalation of alcohol abuse from a gender perspective. Keywords: binge drinking; alcohol; bias; emotion; emotional memory 4 Highlights: Binge drinking is associated with early sex-dependent emotional memory difficulties Female binge drinkers (BDs) show a negative bias in episodic memory An increased bias impairs learning of neutral and positive items in female BDs Females may be more vulnerable to alcohol-related emotional disturbances 5 1.Introduction Adolescence and young adulthood represent “the roller-coaster years”: a tumultuous period characterized by risky behaviour and heightened emotional reactivity (Ahmed, BittencourtHewitt, Sebastian, 2015). These stereotypical behaviours are accompanied by significant emotional and cognitive development driven by asynchronous neuromaturational trajectories (Blakemore, 2008). Indeed, the imbalance between cortical and subcortical circuitry (e.g. subcortical regions such as the amygdala reach maturity much earlier than the prefrontal cortex) contributes to the emergence of mood disorders and substance abuse during adolescence (Fuhrmann, Knoll, Blakemore, 2015). At the same time, this relative immaturity seems to involve greater vulnerabilityin comparison to adulthoodto disruptive events in the brain such as binge drinking (BD) (Silveri et al., 2016). This pattern of repeated intoxications is usually defined as the consumption of a large amount of alcohol within a short period of time, leading to a blood alcohol concentration of at least 0.8 g/l (National Institute on Alcohol Abuse and Alcoholism [NIAAA], 2004). BD peaks during late adolescence (Merill and Carey, 2016) and it is particularly prevalent among young people –one in three young Europeans and North Americans engage in frequent BD (Kraus et al., 2016; Substance Abuse and Mental Health Services Administration [SAMHSA], 2016). Over the last decade, an increasing number of studies have shown that BD is associated with neuroanatomical alterations (e.g. lower volume in prefrontal and hippocampal regions) accompanied by neuropsychological deficits such as difficulties in inhibitory control and verbal episodic memory, particularly in consolidation process (Carbia et al., 2018; Silveri et al., 2016). Although the effects of BD in cold cognition have been thoroughly investigated, emotional functioning –on the contraryhas been relatively unexplored. This gap is somewhat surprising since emotional and social disturbances play a crucial role in the 6 escalation of alcohol use (Hardee et al., 2017; Koob and Volkow, 2016; Zhang and Volkow, 2019). Patients with alcohol use disorders (AUDs) display deficits in the interpretation of emotional intonations, the attribution of mental states to others (theory of mind) and the recognition of emotions from facial expressions (e.g. decoding and overestimation of negative emotions) (Bora and Zorlu, 2017; Oscar-Berman and Bowirrat, 2005). Such deficits have been linked to interpersonal difficulties, emotional dysregulation and increased alcohol consumption and may be an underlying factor leading to the development and maintenance of AUD (Sawyer et al., 2019). Preliminary findings in BDs, suggest difficulties in decoding emotions and -more specificallyin processing negative stimuli (Connell, Patton, McKillop, 2015; Lannoy et al., 2018; Lannoy et al., 2019; Maurage et al., 2013). Despite marked sex differences in brain growth trajectories during adolescence (Hardee et al., 2017), sex-related differences are another poorly studied aspect. In fact, more than one third of the neuropsychological studies in BDs have not analysed sex-dependent effects (e.g. no mention of sex as a covariable; Carbia et al., 2018). In addition, there is substantial evidence for sex differences in vulnerability to alcohol addiction, with internalizing factors such as emotional disturbances (i.e. negative reinforcement; Koob and Volkow, 2016) contributing more to female risk (Hardee et al., 2017). Thus, the effects of BD in emotional functioning, from a gender perspective, deserve further attention. In this sense, we were interested in investigating –for the first timethe association between BD and emotional memory. During adolescence and young adulthood, individuals tend to form strong long-lasting memories, and this is especially true for emotional memories. Events that occurred throughout this period of life are remarkably over-represented in memory (i.e. reminiscence bump), suggesting a sensitive period for mnemonic capacity (Fuhrmann, Knoll, Blakemore, 2015). Emotional episodic memory involves the ability to learn, store, and retrieve information about events or experiences with emotional significance 7 (LaBar and Cabeza, 2006). The formation of new emotional memories has been consistently linked to brain regions undergoing profound neuromaturational changes during adolescence including the bilateral amygdala, anterior hippocampus and prefrontal cortex (PFC) (Murty et al., 2010). In particular, the amygdala and the hippocampus follow sexually dimorphic developmental trajectories (Fish et al., 2019). Considering both that excessive alcohol use has been found to disrupt these structures (Ewing, Sakhardande and Blakemore, 2014; OscarBerman and Bowirrat, 2005) and that emotional memory plays a critical role in life (biased recollection guiding future thinking, self-referential processing, etc.), the aim of this study was to explore potential emotional memory biases in BDs. In order to ensure the stability of alcohol use patterns, we followed university students during two years (18-20 years old) and, at the end of the follow-up, we assessed their performance in an emotional list-learning paradigm. Given that this is the first study to examine emotional memory in alcohol use, our a priori hypothesis is based on both the (I) results from emotional deficits (across different paradigms; Bora and Zorlu, 2017) found in alcoholics and BDs and the (II) expected performance in this type of task in other populations (Durand, Isaac and Januel, 2019). We hypothesize that BDs -especially femaleswill display an emotional memory bias for salient negative stimuli. As emotional memory biases tend to increase with time (after post-encoding process), we predict greater negative bias in delayed recall due to an amplification effect in consolidation process. 2.Material and Methods 2.1 Participants A total of 180 (84 males and 96 females) healthy college students (part of a larger cohort) were followed during two years (18-20 years old) and their alcohol consumption and other drug use was recorded. The individuals gave their written informed consent and received 8 monetary compensation for participation. This study was approved by the Bioethics Committee of the Universidade de Santiago de Compostela, according to the principles expressed in the Declaration of Helsinki. 2.2 General Procedure In this prospective study we recruited first-year university students through an anonymous questionnaire administered in the classroom, including the Alcohol Use Disorders Identification Test (AUDIT) (Babor et al., 2001) and other questions about substance use and health-related behaviours. All participants who were 18 years old, did not report having consumed any illegal drug in the last 6 months and showed their interest in collaborating by providing a contact method (phone or e-mail) were invited to participate in the study. In order to select a sample of healthy college students, students who accepted to participate underwent a screening interview and the following exclusion criteria were applied: history of neurological disorders or severe conditions that affect neurocognitive functioning; history of major psychiatric disorders including alcohol use disorders; current psychopathological symptoms as assessed by the Symptom Checklist-90-R (SCL-90-R) (Degoratis, 1983; Spanish version González de Rivera, et al., 1989). Participants were excluded if they had scores above 90th in the Global Severity Index (GSI); presented motor or sensory deficits; reported regular consumption of psychoactive medications; had family history of alcoholism (two or more first degree relatives or three or more first/second degree relatives); or family history of psychopathology (i.e. major psychopathological disorder such as depression, anxiety or schizophrenia diagnoses in first degree relatives). One hundred and eighty participants completed the two years follow-up. First, they underwent a baseline evaluation in which information regarding their alcohol consumption patterns was recorded. In particular we administered the AUDIT and an alcohol consumption 9 calendar comprising 180 days prior to the evaluation (Alcohol Timeline Followback [TLFB], Sobell and Sobell, 1995). A binge drinking episode was defined as 4/6 standard drinks (or more) for females and males respectively (NIAAA 2004: in Spain a standard drink contains 10 grams of alcohol). In addition, participants also completed a cannabis consumption calendar (TLFB) comprising 90 days prior to the evaluation. Two years later, the same participants underwent a follow-up in which a neuropsychological assessment was performed and again their alcohol consumption and drug use as well as psychopathological symptoms were recorded (Global Severity Index [GSI], Brief Symptom Inventory [BSI-18], Degoratis, 2000; Spanish version, Andreu et al., 2008). 2.3 Material During the follow-up assessment, participants completed a list learning task based on the Emotional Verbal Learning Test (EVLT) (Strauss and Allen, 2013). Apart from yielding traditional memory scores, this task allows for an evaluation of the preferential processing of specific emotional content. The task consists of remembering a list of 18 words (List A), composed by six emotional words from three emotional categories (neutral, positive and negative). These words are read out loud in three consecutive trials. After each trial the subject is asked to recall as many of the words as possible. An interference list (List B) was then presented and free-recall tested (18 new words neutral, positive and negative). The subject was then again asked to recall the words on list A without these words having been presented a second time (Trial IV). After 30 minutes, subjects were asked for their free recall of list A (Trial V) and list B and were then given a recognition task, consisting of a list of 60 words formed by the words from List A, the words from List B and phonologically or semantically similar words (distractors). Participants had to indicate if a word was from list A, list B or none of them (recognition memory trial). The characteristics of the task (longterm recall of both lists, increased numbers of words in comparison with the RAVLT [Rey, 16 related effects on emotional bias would be enhanced, reflecting a strengthening of the memory trace that is disproportional to memory importance (Hamann, 2001). One potential limitation of this study is the assessment of long-term recall only after a 30 min delay (typical delay in list-leaning paradigms), which could be reducing the intensity of the observed bias. Another potential limitation is the lack of a neuropsychological assessment of participants before they first engaged in BD, which prevents us from discounting the possibility of pre-existing memory biases. Emotional memory biases can negatively influence future thinking and self-referential processing (e.g. rumination; Nandrino, Gandolphe, El Haj, 2017), especially memories formed during the sensitive period of adolescence known as reminiscence bump (Fuhrmann, Knoll, Blakemore, 2015). Thus, future studies should further investigate the effects of BD on emotional memory (e.g. by increasing the length of time for recall; by examining the effects under alcohol intoxication or by exploring the mediating role of stress hormones), as well as focus on specific types of memory such as autobiographical memory or source memory (Morgan, Riccelli, Maitland, Curran, 2004; Nandrino, Gandolphe, El Haj, 2017). 4.1. Conclusion This study provides novel information indicating that female BDs -but not malesdisplay an alcohol-related mnemonic increase of negative information in episodic memory, at the expenses of less memorization of neutral information. The results highlight early sexdependent alterations in BDs regarding emotional memory bias. A malfunction in this - otherwise adaptive processcould offer new insights into the theory that females may be more vulnerable to addiction risk through an emotion-mediated pathway. 17 References Ahmed, S. P., Bittencourt-Hewitt, A., Sebastian, C. L., 2015. Neurocognitive bases of emotion regulation development in adolescence. Dev Cogn Neurosci. 15, 11-25. doi: 10.1016/j.dcn.2015.07.006. Aloi, J., Blair, K. S., Crum, K. I., Meffert, H., White, S. F., Tyler, P. M., Thornton, L.C., Mobley, A. M., Killanin, A. D., Adams, K. O., Filbey, F., Pope, K., Blair, R.J.R.,.,2018. Adolescents show differential dysfunctions related to Alcohol and Cannabis Use Disorder severity in emotion and executive attention neuro-circuitries. Neuroimage Clin. 19, 782-792. doi: 10.1016/j.nicl.2018.06.005. Andreu, Y., Galdón, M. J., Dura, E., Ferrando, M., Murgui, S., García, A., & Ibáñez, E., 2008. Psychometric properties of the Brief Symptoms Inventory-18 (BSI-18) in a Spanish sample of outpatients with psychiatric disorders. Psicothema, 20, 844-850. Babor, T.F, Higgins-Biddle, J.C, Saunders, J.B, Monteiro, M.G., 2001. AUDIT. The Alcohol Use Disorders Identification Test. Guidelines for Use in Primary Health Care, 2nd ed. Geneva: World Health Organization. Besken, M., Gülgöz, S., 2008. Reliance on schemas in source memory: Age differences and similarity of schemas. Aging, Neuropsychology, and Cognition. 16, 1-21. doi: 10.1080/13825580802175650. Blakemore, S. J., 2008. The social brain in adolescence. Nat. Rev. Neurosci., 9, 267–277. doi:10.1038/nrn2353 18 Bogie, B. J., Persaud, M. R., Smith, D., Kapczinski, F. P., Frey, B. N., 2019. Explicit Emotional Memory Biases in Mood Disorders: A Systematic Review. Psychiatry Res. 278, 162-172. doi: 10.1016/j.psychres.2019.06.003. Bora, E., Zorlu, N.,2017. Social cognition in alcohol use disorder: a meta‐analysis. Addiction 112, 40-48. doi: 10.1111/add.13486. Carbia, C., López-Caneda, E., Corral, M., & Cadaveira, F., 2018. A systematic review of neuropsychological studies involving young binge drinkers. Neurosci. Biobehav. Rev.90, 332-349. doi: 10.1016/j.neubiorev.2018.04.013. Cohen-Gilbert, J. E., Nickerson, L. D., Sneider, J. T., Oot, E. N., Seraikas, A. M., Rohan, M. L., & Silveri, M. M., 2017. College binge drinking associated with decreased frontal activation to negative emotional distractors during inhibitory control. Front Psychol. 8, 1650. doi: 10.3389/fpsyg.2017.01650. Connell, A. M., Patton, E., McKillop, H., 2015. Binge drinking, depression, and electrocortical responses to emotional images. Psychol Addict Behav. 29, 673–682. doi: 10.1037/adb0000071. Degoratis, L.R., SCL-90-R. 1983. Administration, scoring and procedures manual II for the revised version of the SCL-90-R. Baltimore: John Hopkins University Press. Derogatis, L. R. 2001. BSI 18, Brief Symptom Inventory 18: Administration, scoring and procedures manual. NCS Pearson, Incorporated. Dolcos, F., Katsumi, Y., Weymar, M., Moore, M., Tsukiura, T., Dolcos, S., 2017. Emerging directions in emotional episodic memory. Front Psychol. 8, 1867. doi: 10.3389/fpsyg.2017.01867. 19 Durand, F., Isaac, C., & Januel, D., 2019. Emotional Memory in Post-traumatic Stress Disorder: A Systematic PRISMA Review of Controlled Studies. Front Psychol. 5, 303. doi: 10.3389/fpsyg.2019.00303. Ewing, S. W. F., Sakhardande, A., & Blakemore, S. J.,2014. The effect of alcohol consumption on the adolescent brain: A systematic review of MRI and fMRI studies of alcohol-using youth. Neuroimage Clin. 5, 420-37. doi: 10.1016/j.nicl.2014.06.011. Fish, A. M., Nadig, A., Seidlitz, J., Reardon, P. K., Mankiw, C., McDermott, C. L., ... & Chakravarty, M. M., 2019. Sex-Biased Trajectories of Amygdalo-Hippocampal Morphology Change Over Human Development. Neuroimage 27, 116122. doi: 10.1016/j.neuroimage.2019.116122 Fuhrmann, D., Knoll, L. J., & Blakemore, S. J., 2015. Adolescence as a sensitive period of brain development. Trends Cogn. Sci.19, 558-566. doi: 10.1016/j.tics.2015.07.008. Gibbons, R.D., Hedeker, D., DuToit, S., 2010. Advances in analysis of longitudinal data. Annu. Rev. Clin. Psychol. 6, 79–107. doi:10.1146/annurev.clinpsy. 032408.153550. González de Rivera, J. L., Derogatis, L.R., de las Cuevas, C., Gracia Marco, R., RodríguezPulido, F., Henry-Benítez, M., Monterrey, A. L., 1989. The spanish version of the SCL-90-R. Normative data in thegeneral population. Clinical Psychometric Research, Towson. Hale, C., Last, B. S., Meier, I. B., Yeung, L. K., Budge, M., Sloan, R. P., Small, S. A., Brickman, A. M., 2017. The ModRey: An Episodic Memory Test for Nonclinical and Preclinical Populations. Assessment. 26,1154-1161. doi: 10.1177/1073191117723113 Hamann, S., 2001. Cognitive and neural mechanisms of emotional memory. Trends Cogn Sci. 5, 394-400. doi: 10.1016/S1364-6613(00)01707-1 20 Hardee, J. E., Cope, L. M., Munier, E. C., Welsh, R. C., Zucker, R. A., & Heitzeg, M. M., 2017. Sex differences in the development of emotion circuitry in adolescents at risk for substance abuse: a longitudinal fMRI study. Soc. Cogn. Affect. Neurosci. 12, 965-975. doi: 10.1093/scan/nsx021. Hardee, J. E., Cope, L. M., Munier, E. C., Welsh, R. C., Zucker, R. A., Heitzeg, M. M.,2017. Sex differences in the development of emotion circuitry in adolescents at risk for substance abuse: a longitudinal fMRI study. Soc. Cogn. Affect. Neurosci.12, 965-975. doi: 10.1093/scan/nsx021. Hu, S., Ide, J. S., Chao, H. H., Zhornitsky, S., Fischer, K. A., Wang, W., Zhang, S., Li C.R.,2018. Resting state functional connectivity of the amygdala and problem drinking in non-dependent alcohol drinkers. Drug Alcohol Depend. 185,173-180. doi: 10.1016/j.drugalcdep.2017.11.026. Koob, G. F., Volkow, N. D., 2016. Neurobiology of addiction: a neurocircuitry analysis. Lancet Psychiatry 3, 760-773. doi: 10.1016/S2215-0366(16)00104-8. Kraus, L., Guttormsson, U., Leifman, H., Arpa, S., Molinaro, S., Monshouwer, K., Hibell, B. 2016. ESPAD Report 2015. Results from the European School Survey Project on Alcohol and Other Drugs. Lisbon: European Monitoring Centre for Drugs and Drug Addiction and the European School Survey Project on Alcohol and Other Drugs. LaBar, K. S., Cabeza, R., 2006. Cognitive neuroscience of emotional memory. Nat Rev Neurosci. 7, 54-64. doi:10.1038/nrn1825 Lannoy, S., Benzerouk, F., Maurage, P., Barriere, S., Billieux, J., Naassila, M.,Kaladjian, A., Gierski, F., 2019. Disrupted Fear and Sadness Recognition in Binge Drinking: A Combined 21 Group and Individual Analysis. Alcohol Clin. Exp. Res.43, 1978-1985. doi: 10.1111/acer.14151. Lannoy, S., D’Hondt, F., Dormal, V., Blanco, M., Brion, M., Billieux, J., Campanella, S., Maurage, P., 2018. Electrophysiological correlates of emotional crossmodal processing in binge drinking. Cogn. Affect. Behav. Neurosci. 18, 1076–1088. doi: 10.3758/s13415-0180623-3. Maurage, P., Bestelmeyer, P.E.G., Rouger, J., Charest, I., Belin, P., 2013. Binge drinking influences the cerebral processing of vocal affective bursts in young adults. Neuroimage Clin 3, 218–225. doi: 10.1016/j.nicl.2013.08.010 Merrill, J.E., Carey, K.B., 2016. Drinking over the lifespan: focus on college ages. Alcohol Res. 38, 103–114. Morgan, C. J., Riccelli, M., Maitland, C. H., & Curran, H. V., 2004. Long-term effects of ketamine: evidence for a persisting impairment of source memory in recreational users. Drug Alcohol Depend. 75, 301-308. Doi: 10.1016/j.drugalcdep.2004.03.006 Murty, V. P., Ritchey, M., Adcock, R. A., LaBar, K. S.,2010. fMRI studies of successful emotional memory encoding: A quantitative meta-analysis. Neuropsychologia 48, 34593469. doi: 10.1016/j.neuropsychologia.2010.07.030. Nandrino, J. L., Gandolphe, M. C., El Haj, M. 2017. Autobiographical memory compromise in individuals with alcohol use disorders: Towards implications for psychotherapy research. Drug Alcohol Depend. 179, 61-70. doi: 10.1016/j.drugalcdep.2017.06.027. Epub 2017 Jul 21. National Institute of Alcohol Abuse, Alcoholism, 2004. NIAAA council approves definition of binge drinking. NIAAA Newslett. p. 3. Available from: http://pubs.niaaa.nih.gov/ publications/Newsletter/winter2004/Newsletter_Number3.pdf. 22 Oscar-Berman, M., Bowirrat, A., 2005. Genetic influences in emotional dysfunction and alcoholism-related brain damage. Neuropsychiatr Dis Treat. 1, 211-229. Peltier, M. R., Verplaetse, T. L., Mineur, Y. S., Petrakis, I. L., Cosgrove, K. P., Picciotto, M. R., & McKee, S. A., 2019. Sex differences in stress-related alcohol use. Neurobiol Stress. 10, 100149. doi: 10.1016/j.ynstr.2019.100149. Redondo, J., Fraga, I., Padrón, I., Comesaña, M., 2007. The Spanish adaptation of ANEW (affective norms for English words). Behav. Res. Methods. 39, 600-605. doi:10.3758/BF03193031 Rey A., 1964. L’examen clinique en psychologie. Paris: Presses Universitaires de France Sawyer, K. S., Maleki, N., Urban, T., Marinkovic, K., Karson, S., Ruiz, S. M., Harris, G. J., Oscar-Berman, M., 2019. Alcoholism gender differences in brain responsivity to emotional stimuli. ELife 8, e41723. doi: 10.7554/eLife.41723. Silveri, M.M., Dager, A.D., Cohen-Gibert, J.E., Sneider, J.T., 2016. Neurobiological signatures associated with alcohol and drug use in the human adolescent brain. Neurosci. Biobehav. Rev. 70, 244–259. doi:10.1016/j.neubiorev.2016.06.042. Sobell, L.C. Sobell, M.B., 1995. Alcohol Timeline Followback Users’ Manual. Toronto, Canada: Addiction Research Foundation. Spear, L. P., 2015. Adolescent alcohol exposure: are there separable vulnerable periods within adolescence?. Physiol Behav.148, 122-130. doi: 10.1016/j.physbeh.2015.01.027. Stephens, D.N., Duka, T., 2008. Cognitive and emotional consequences of binge drinking: role of amygdala and prefrontal cortex.Philos Trans R Soc Lond B Biol Sci. 3633, 169-79. doi: 10.1098/rstb.2008.0097. 23 Strauss, G. P., & Allen, D. N., 2013. Emotional Verbal Learning Test: development and psychometric properties. Arch Clin Neuropsychol. 28, 435-451. doi: 10.1093/arclin/act007. Substance Abuse and Mental Health Services Administration (SAMHSA). Key Substance Use and Mental Health Indicators in the United States: Results from the 2015 National Survey on Drug Use and Health (HHS Publication No. SMA 16-4984, NSDUH Series H-51) Townshend, J.M., Duka, T., 2003. Mixed emotions: alcoholics’ impairments in the recognition of specific emotional facial expressions. Neuropsychologia, 41, 773–782. doi:10.1016/S0028-3932(02)00284-1 Zachry, J. E., Johnson, A. R., Calipari, E. S., 2019. Sex Differences in Value-Based Decision Making Underlie Substance Use Disorders in Females. Alcohol Alcohol. 54, 339-341. doi: 10.1093/alcalc/agz052. Zhang, R., Volkow, N. D., 2019. Brain default-mode network dysfunction in addiction. Neuroimage 15,313-331. doi: 10.1016/j.neuroimage.2019.06.036. 24 Tables Table 1. Mean values (and standard deviations) for demographical and clinical data at baseline and follow-up. Baseline Follow-up Males (N=84) Females (N=96) Males (N=84) Females (N=96) Age 18.02 (0.18) 18.00 (0.00) 19.89 (0.32) 19.93 (0.25) AUDIT Total 6.33 (5.10) 6.45 (5.70) 6.36 (4.81) 6.15 (5.31) AUDIT-C 3.87 (2.70) 3.74 (2.67) 3.95 (2.64) 3.63 (2.45) Age of drinking onset 15.70 (1.26) 15.71 (1.23) Maximum drinks a,b 12.17 (8.37) 10.17 (7.38) 10.32 (6.59) 8.98 (6.74) Number of BD episodes a 13.14 (13.90) 16.96 (17.10) 14.52 (14.72) 17.13 (16.89) Number of cannabis days c 3.90 (11.55) 12.39 (18.19) 5.65 (15.20) 18.51 (21.69) Tobacco smokers * 6 19 15 31 GSI (SCL90-R) 51.73 (24.82) 53.02 (25.78) GSI (BSI-18)* 0.40 (0.31) 0.53 (0.39) a Timeline Follow Back (TLFB) alcohol 180 days. b Measure as maximum number of standard drink units on a drinking occasion. c TLFB cannabis 90 days * P ≤ 0.05 GSI= Global Severity Index. 25 Table 2. Means (and standard deviations) for emotional memory performance. Males (n=84) Females (n=96) Total list A (I-III) 36.20 (5.47) 38.80 (4.54) Neutral 12.18 (2.70) 13.13 (1.91) Positive 11.37 (2.30) 12.41 (2.32) Negative 12.65 (2.35) 13.26 (2.15) Total List B 8.25 (2.34) 8.88 (2.26) Immediate List A (IV) 12.24 (2.59) 13.24 (2.59) Neutral 4.53 (1.30) 4.80 (1.11) Positive 3.81 (1.20) 4.39 (1.24) Negative 3.90 (1.32) 4.04 (1.18) Delayed List A (V) 12.40 (2.60) 13.57 (2.52) Neutral 4.57 (1.23) 4.85 (0.98) Positive 3.84 (1.20) 4.43 (1.18) Negative 3.99 (1.32) 4.29 (1.17) Delayed list B 4.47 (2.60) 5.45 (2.58) Recognition list A 15.51 (2.17) 16.14 (1.67) Intrusions 2.58 (2.72) 2.42 (2.48) False alarms 12.58 (5.40) 10.56 (4.68)