Examining predictors of cocaine withdrawal syndrome at the end of detoxification treatment in women with cocaine use disorder.

BACKGROUND: Detoxification is frequently recommended as a treatment for moderate to severe Cocaine Use Disorder (CUD). However, the response to detoxification varies among patients, and previous studies have focused mostly on patterns of drug use behavior to test associations with treatment outcomes, overlooking the potential impact of psychosocial factors, other clinical variables, and individual life experiences. In this study we comprehensively examined several variables aiming to find the most relevant predictors to classify patients with severe versus non-severe cocaine withdrawal symptoms at the end of detoxification. METHODS: Data from 284 women with CUD who enrolled in a 3-week detoxification program was used in this longitudinal study. Psychosocial, clinical, and drug use behavior characteristics were evaluated, generating a dataset with 256 potential predictors. We tested six different machine learning classification algorithms. RESULTS: The best classification algorithm achieved an average accuracy and ROC-AUC of approximately 70%. The 16 features selected as best predictors were the severity of psychiatric, family, and social problems and the level of exposure to childhood maltreatment. Features associated with drug-use behavior included days consuming drugs and having craving symptoms in the last month before treatment, number of previous drug/alcohol-related treatments, and a composite score of addiction severity. The level of cocaine withdrawal syndrome at the beginning of detoxification was also a key feature for classification. A network analysis revealed the pattern of association between predictors. CONCLUSION: These variables can be assessed in real-world clinical settings, potentially helping clinicians to identify individuals with severe cocaine withdrawal that is likely to be sustained over the course of detoxification.

Correction: The psychological impact of the COVID-19 pandemic in Portugal: The role of personality traits and emotion regulation strategies.

[This corrects the article DOI: 10.1371/journal.pone.0269496.].

To produce or not to produce? Contrasting the effect of substance abuse in social decision-making situations.

Substance use disorders (SUD) have been related to high criminal justice costs, expensive healthcare, social impairment, and decision-making deficits. In non-social decision-making tasks, people with SUD tend to take more risks and choose small immediate rewards than controls. However, few studies have explored how people with SUD behave in social decision-making situations where the resources and profits depend directly on participants' real-time interaction, i.e., social foraging situations. To fulfill this gap, we developed a real-time interaction task to (a) compare the proportion of producers (individuals who tend to search for food sources) and scroungers (individuals who tend to steal or join previously discovered food sources) among participants with SUD and controls with respect to the optimal behavior predicted by the Rate Maximization Model, and (b) explore the relationship between social foraging strategies, prosocial behavior, and impulsivity. Here participants with SUD (n = 20) and a non-user control group (n = 20) were exposed to the Guaymas Foraging task (GFT), the Social Discounting task (SD), and the Delay Discounting task (DD). We found that participants in the control group tended to produce more and obtain higher profits in contrast to substance abuser groups. Additionally, SD and DD rates were higher for scroungers than producers regardless of the group. Our results suggest that producers tend to be more altruistic and less impulsive than scroungers. Knowing more about social strategies and producers' characteristics could help develop substance abuse prevention programs.

Non-pharmacological treatment-related changes of molecular biomarkers in major depressive disorder: A systematic review and meta-analysis

Background: Major depressive disorder (MDD) is a serious mood disorder and leading cause of disability. Despite treatment advances, approximately 30% of individuals with MDD do not achieve adequate clinical response. Better understanding the biological mechanism(s) underlying clinical response to specific psychopharmacological interventions may help fine tune treatments in order to further modulate their underlying mechanisms of action. However, little is known regarding the effect of non-pharmacological treatments (NPTs) on candidate molecular biomarker levels in MDD. This review aims to identify molecular biomarkers that may elucidate NPT response for MDD. Methods: We performed a systematic review and a multilevel linear mixed-effects meta-analyses, and a meta-regression. Searches were performed in PubMed, Scopus, and PsycINFO in October 2020 and July 2021. Results: From 1387 retrieved articles, 17 and six studies were included in the systematic review and meta-analyses, respectively. Although there was little consensus associating molecular biomarker levels with symptomology and/or treatment response, brain metabolites accessed via molecular biomarker-focused neuroimaging techniques may provide promising information on whether an individual with MDD would respond positively to NPTs. Furthermore, non-invasive brain stimulation interventions significantly increased the expression of neurotrophic factors (NTFs) compared to sham/placebo, regardless of add-on pharmacological treatment. Conclusions: NTFs are candidate biomarkers to fine-tune NIBS for MDD treatment. (AU)

A Longitudinal Investigation of Blood Neurofilament Light Chain Levels in Chronic Cocaine Users.

The identification of a blood marker of brain pathology that is sensitive to substance-induced neurotoxicity and dynamically responds to longitudinal changes in substance intake would substantially improve clinical monitoring in the field of substance use and addiction. Here, we explored the hypothesis that plasma levels of neurofilament light chain (NfL), a promising marker of neuroaxonal pathology, are elevated in chronic cocaine users and longitudinally associated with changes in cocaine use. Plasma NfL levels were determined using single molecule array (SIMOA) technology at baseline and at a 4-month follow-up. Substance use was subjectively assessed with an extensive interview and objectively measured via toxicological analysis of urine and 4-month hair samples. In a generalized linear model corrected for sex, age, and body mass index, NfL plasma levels were elevated in cocaine users (n=35) compared to stimulant-naïve healthy controls (n=35). A positive correlation between cocaine hair concentration and NfL levels was also found. Changes in cocaine hair concentration (group analysis of increasers vs. decreasers) over the 4-month interval predicted NfL levels at follow-up, indicating a rise in NfL with increased cocaine use and a reduction with decreased use. No associations between use or change of use of other substances (including the neurotoxic cocaine adulterant levamisole) and NfL levels were found. Our findings demonstrate that NfL is a sensitive marker for assessing cocaine-related neuroaxonal pathology, supporting the utility of blood NfL analysis in addiction research but also suggesting the detailed assessment of substance use in neurological studies and diagnostics.

Non-pharmacological treatment-related changes of molecular biomarkers in major depressive disorder: A systematic review and meta-analysis.

Background: Major depressive disorder (MDD) is a serious mood disorder and leading cause of disability. Despite treatment advances, approximately 30% of individuals with MDD do not achieve adequate clinical response. Better understanding the biological mechanism(s) underlying clinical response to specific psychopharmacological interventions may help fine tune treatments in order to further modulate their underlying mechanisms of action. However, little is known regarding the effect of non-pharmacological treatments (NPTs) on candidate molecular biomarker levels in MDD. This review aims to identify molecular biomarkers that may elucidate NPT response for MDD. Methods: We performed a systematic review and a multilevel linear mixed-effects meta-analyses, and a meta-regression. Searches were performed in PubMed, Scopus, and PsycINFO in October 2020 and July 2021. Results: From 1387 retrieved articles, 17 and six studies were included in the systematic review and meta-analyses, respectively. Although there was little consensus associating molecular biomarker levels with symptomology and/or treatment response, brain metabolites accessed via molecular biomarker-focused neuroimaging techniques may provide promising information on whether an individual with MDD would respond positively to NPTs. Furthermore, non-invasive brain stimulation interventions significantly increased the expression of neurotrophic factors (NTFs) compared to sham/placebo, regardless of add-on pharmacological treatment. Conclusions: NTFs are candidate biomarkers to fine-tune NIBS for MDD treatment.

Validation of the Brazilian Portuguese version of the Quick Inventory of Depressive Symptomatology and Self-Report (QIDS-SR16) for the Brazilian population.

OBJECTIVES: To evaluate the psychometric properties of the Quick Inventory of Depressive Symptomatology (QID-SR16), a self-report instrument based on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria that assesses the severity of depression symptoms, in the Brazilian population. METHODS: Participants were 4,400 Brazilians over the age of 15 years recruited for an online survey assessing depressive symptoms during the early phase of the coronavirus disease 2019 (COVID-19) pandemic in Brazil. The internal consistency, construct validity, and convergent and discriminant validity of the QIDS-SR16 were evaluated. RESULTS: The model tested was considered an adequate fit to the data (comparative fit index [CFI] = 0.947, Tucker-Lewis index [TLI] = 0.927, and root-mean-square error of approximation [RMSEA] = 0.051) and its internal consistency was good, with a Cronbach's alpha of 0.71 and an average item correlation of 0.23. The correlations between the total QIDS-SR16 score and the total scores of the Patient Health Questionnaire (PHQ-9) instruments (r = 0.67, p < 0.001), the Posttraumatic Symptoms Checklist (PCL-5) (r = 0.61, p < 0.001), and the Patient-Reported Outcomes Measurement Information System (PROMIS) (r = 0.60, p < 0.001) indicate good concurrent and convergent validity. CONCLUSION: The QIDS-SR16 has robust psychometric properties in terms of its internal consistency, construct validity, and convergent and discriminant validity. The Portuguese version of the QIDS-SR16 is an adequate instrument for assessment of depressive symptoms in the context of an online survey.

Decision-making under risk and theory of mind in adolescent offenders in provisional deprivation of liberty.

INTRODUCTION: Delinquent behaviors are risky behaviors that increase during puberty and reach their highest peak in late adolescence. It has been proposed that poor decision-making and theory of mind (ToM) are key cognitive processes implicated with delinquency during adolescence, affecting evaluation of risks and impairing appreciation of social norms. Nevertheless, it is not yet clear whether adolescent offenders who are subjected to provisional deprivation of liberty due to conflict with the law (adolescents in conflict with the law [ACL]) might, in fact, present a specific profile with regard to these cognitive processes. OBJECTIVES: To assess deliberative decision-making and ToM among adolescents in conflict with the law and adolescents not in conflict with the law. METHODS: The sample comprised 62 participants: ACL (n = 29) and a control group (CG) (n = 33). ToM was assessed with the Reading the Mind in the Eyes Test (RMET) and decision-making was assessed with the Columbia Card Task (CCT). Substance use, callous-unemotional traits, childhood maltreatment, and intelligence quotient (IQ) were also assessed. RESULTS: ACL had more ToM errors for negative mental states in comparison to CG, but not for error rates concerning neutral and positive mental states. With regards to decision-making, our results suggest that ACL group members did not vary their behavior based on the available information and that the risk information had an opposite effect on the number of cards chosen (risk-taking behavior) when compared to CG. CONCLUSION: These findings have important implications for development of interventions for these adolescents, suggesting that they tend to learn little from negative outcomes and have reduced capacity to process negative emotions.

Validation of the Brazilian Portuguese version of the Quick Inventory of Depressive Symptomatology and Self-Report (QIDS-SR16) for the Brazilian population

Abstract Objectives To evaluate the psychometric properties of the Quick Inventory of Depressive Symptomatology (QID-SR16), a self-report instrument based on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria that assesses the severity of depression symptoms, in the Brazilian population. Methods Participants were 4,400 Brazilians over the age of 15 years recruited for an online survey assessing depressive symptoms during the early phase of the coronavirus disease 2019 (COVID-19) pandemic in Brazil. The internal consistency, construct validity, and convergent and discriminant validity of the QIDS-SR16 were evaluated. Results The model tested was considered an adequate fit to the data (comparative fit index [CFI] = 0.947, Tucker-Lewis index [TLI] = 0.927, and root-mean-square error of approximation [RMSEA] = 0.051) and its internal consistency was good, with a Cronbach's alpha of 0.71 and an average item correlation of 0.23. The correlations between the total QIDS-SR16 score and the total scores of the Patient Health Questionnaire (PHQ-9) instruments (r = 0.67, p < 0.001), the Posttraumatic Symptoms Checklist (PCL-5) (r = 0.61, p < 0.001), and the Patient-Reported Outcomes Measurement Information System (PROMIS) (r = 0.60, p < 0.001) indicate good concurrent and convergent validity. Conclusion The QIDS-SR16 has robust psychometric properties in terms of its internal consistency, construct validity, and convergent and discriminant validity. The Portuguese version of the QIDS-SR16 is an adequate instrument for assessment of depressive symptoms in the context of an online survey.

Cue-induced cocaine craving enhances psychosocial stress and vice versa in chronic cocaine users.

Stress and craving, it has been found, contribute to the development and maintenance of and relapse in cocaine use disorder. Chronic cocaine users (CU), previous research has shown, display altered physiological responses to psychosocial stress and increased vegetative responding to substance-related cues. However, how psychosocial stress and cue-induced craving interact in relation to the CU's physiological responses remains largely unknown. We thus investigated the interaction between acute psychosocial stress and cocaine-cue-related reactivity in 47 CU and 38 controls. In a crossed and balanced design, the participants were randomly exposed to a video-based cocaine-cue paradigm and the Trier Social Stress Test (TSST) or vice versa to investigate possible mutually augmenting effects of both stressors on physiological stress responses. Over the course of the experimental procedure, plasma cortisol, ACTH, noradrenaline, subjective stress, and craving were assessed repeatedly. To estimate the responses during the cocaine-cue paradigm and TSST, growth models and discontinuous growth models were used. Overall, though both groups did not differ in their endocrinological responses to the TSST, CU displayed lower ACTH levels at baseline. The TSST did not elevate craving in CU, but when the cocaine-cue video was shown first, CU displayed an enhanced cortisol response to the subsequent TSST. In CU, cocaine-cues robustly evoked craving but no physiological stress response, while cue-induced craving was intensified after the TSST. Taken together, though CU did not show an altered acute stress response during the TSST, stress and craving together seemed to have mutually augmenting effects on their stress response.

In- and Out-Group Effects on Social Perception and Empathy in Cocaine Use Disorder.

Earlier research revealed that cocaine users display impairments in emotional but not necessarily in cognitive empathy. However, no study to date has tested whether empathy is generally altered or whether impairments are restricted to specific social targets. The current investigation addresses this open question. In addition, we examined whether attributions of warmth and competence as well as personal future expectancies differed between cocaine users and substance-naïve controls. Twenty-two chronic cocaine users and 40 stimulant-naïve controls specified their perceived warmth and competence for four social targets [in-group member, opposite consumption out-group member (cocaine user for controls and non-user for cocaine user), opposite consumption out-group member of opposite gender, and elderly person]. They also specified their cognitive and emotional empathy for these four targets facing eight desirable and eight undesirable events. Finally, they rated the likelihood of these scenarios happening to themselves. Both cocaine users and controls attributed lower warmth to cocaine-using than non-using targets. Comparably, no in-group preference was observed in cocaine user's emotional empathy ratings, and greater denigration of the in-group was associated with higher frequency and doses of cocaine consumption. In addition, cocaine users rated both desirable and undesirable events as more likely to happen to themselves than did controls. Results show that substance-naïve individuals stigmatize cocaine users. They further point to compromised self-esteem in cocaine users resulting from such stigmatization. Interventions should address stigmatization processes to break the vicious circle of mutual social distancing and stronger dedication to the drug.

The psychological impact of the COVID-19 pandemic in Portugal: The role of personality traits and emotion regulation strategies.

Recent evidence suggests that both personality traits (PT) and emotion regulation (ER) strategies play an important role in the way people cope with the COVID-19 pandemic. The aim of this study was two folded. First, to longitudinally investigate the psychological distress (depression, anxiety, and stress levels) taking in consideration PT and ER strategies in 3 different moments: during the first lockdown period (April/20), at the first deconfinement (May/20) and 1-month after the first deconfinement (Jun/20)-Experiment I. Second, to cross-sectionally evaluate the impact of the pandemic in psychological distress and the correlates with PT and ER 6-months after the first deconfinement November/20 to February/21 -Experiment II. A total of 722 volunteers (Experiment I = 180; Experiment II = 542) aged 18 years or older participated in this online survey. The findings from Experiment I show that psychological distress decreased after the lockdown period, however, neuroticism traits predicted higher levels of depression, anxiety and stress symptoms, while difficulties in ER strategies were identified as a risk factor for depression and stress. For experiment II, neuroticism traits and being infected with COVID-19 were associated to higher levels of symptomatology, while unemployment and the use of emotional suppression strategies to cope with emotional situations were associated to depressive and anxiety symptoms. Although the psychological impact of the COVID-19 outbreak decreased over time in our sample, the current findings suggest that difficulties in emotional regulation and high levels of neuroticism traits might be potential risk factors for psychiatric symptomatology during the COVID-19 pandemic. Thus, people with difficulties in ER and neuroticism traits would benefit from psychological interventions that provide personality-appropriate support and promote emotion regulation skills during stressful events, such as the case of the global pandemic.

The Perceptions of Women About Their High Experience of Using Crack Cocaine.

Introduction: The aim of this study was to explore the perceptions of women about their experience in using crack cocaine, discussing their motivations for using it and the repercussions in their lives. Objective: To investigate these experiences, a qualitative exploratory study was conducted, using the inductive thematic analyses of the content. Methods: Eight female crack cocaine users took part in this study. They were assessed by a semi-structured interview, addressing the crack cocaine use experience. Four main themes emerged in the interviews: (1) crack cocaine "high" experience; (2) symptoms related to crack cocaine use; (3) circumstances of crack cocaine use; and (4) crack cocaine use consequences. Results: The main perceptions reported by the users were related to a feeling of being disconnected to the world preceded by a pleasant experience, especially during the first moments of use. They revealed that the drug fulfills a key role of coping strategy to handle with negative thoughts, emotions or life experiences. An important influence of social issues was reported in relation to the onset of crack cocaine use. Negative consequences and significant impact on their lives appeared in their reports, regarding the loss of family ties, involvement with prostitution, traumatic experiences and violence. Conclusion: Taking together all women's perceptions suggests that beyond the positive immediate rewarding effect, the maintenance of use might be related to the dissociative experience and self-medication role, acting as negative reward by relieving of negative life experiences that, in turn, are both cause and consequence of the drug use.

The Acute Impact of the Early Stages of COVID-19 Pandemic in People with Pre-Existing Psychiatric Disorders: A Systematic Review.

People with pre-pandemic health conditions are more vulnerable and more likely to suffer greater psychosocial impact due to the current COVID-19 pandemic and the lockdown measures. Thus, the objective of this work was to systematically review the impact of the early stages COVID-19 pandemic on people with pre-existing psychiatric disorders. The search was performed between 23 January and 2 September 2021 in PubMed, PsycINFO, and EMBASE. A total of 4167 published results were identified; however, only 49 were included in this review. Results show that there was considerable heterogeneity among studies, which resulted in a low consensus. However, it seems that the impact of the first stage of the COVID-19 pandemic on psychiatric disorders was two-fold: (1) an overall effect, in which people suffering from psychiatric disorders in general experienced more psychological distress and anxiety when compared to people who had no psychiatric diagnosis, and (2) a condition-specific effect, namely in people suffering from eating disorders and obsessive compulsive disorders. Moreover, the current work highlights that there were also some external factors that were related to worsening symptoms. For instance, unemployment or experiencing work and financial difficulties can be a trigger for greater distress during the pandemic for people with mood disorders, and being alone and in social isolation during the COVID-19 pandemic may actually increase substance use and relapse rates. Further studies are needed to prospectively investigate the long-term effects of the current COVID-19 pandemic on people with (pre)-existing psychiatric conditions and on the onset or deterioration of psychiatric-related symptoms in a larger number of participants, as well as exploring the long-term effects of the current pandemic on mental health.

Decision-making under risk and theory of mind in adolescent offenders in provisional deprivation of liberty

Abstract Introduction Delinquent behaviors are risky behaviors that increase during puberty and reach their highest peak in late adolescence. It has been proposed that poor decision-making and theory of mind (ToM) are key cognitive processes implicated with delinquency during adolescence, affecting evaluation of risks and impairing appreciation of social norms. Nevertheless, it is not yet clear whether adolescent offenders who are subjected to provisional deprivation of liberty due to conflict with the law (adolescents in conflict with the law [ACL]) might, in fact, present a specific profile with regard to these cognitive processes. Objectives To assess deliberative decision-making and ToM among adolescents in conflict with the law and adolescents not in conflict with the law. Methods The sample comprised 62 participants: ACL (n = 29) and a control group (CG) (n = 33). ToM was assessed with the Reading the Mind in the Eyes Test (RMET) and decision-making was assessed with the Columbia Card Task (CCT). Substance use, callous-unemotional traits, childhood maltreatment, and intelligence quotient (IQ) were also assessed. Results ACL had more ToM errors for negative mental states in comparison to CG, but not for error rates concerning neutral and positive mental states. With regards to decision-making, our results suggest that ACL group members did not vary their behavior based on the available information and that the risk information had an opposite effect on the number of cards chosen (risk-taking behavior) when compared to CG. Conclusion These findings have important implications for development of interventions for these adolescents, suggesting that they tend to learn little from negative outcomes and have reduced capacity to process negative emotions.

Stability and test-retest reliability of different hormonal stress markers upon exposure to psychosocial stress at a 4-month interval.

The Trier Social Stress Test (TSST) has been shown to reliably induce physiological stress responses in the hypothalamus-pituitary-adrenal (HPA) and in the sympathetic-adrenal-medullary (SAM) axis in cross-sectional studies. However, it was also reported that repeated exposure to the TSST might be associated with habituation, mainly of the HPA axis responsivity. Thus, in all longitudinal stress studies involving repeated TSST administration, potential habituation of the HPA axis response complicates the interpretation of results. The goal of the present study was therefore to assess stability and test-retest reliability of a number of different endocrinological stress markers as well as subjective stress responses after two exposures to the TSST four months apart. We assessed salivary and plasma cortisol profiles, plasma ACTH and noradrenaline profiles, as well as subjective stress ratings in healthy volunteers before, during, and after the TSST at six time-points both at test-day 1 (TSST_1, n = 42) and test-day 2 (TSST_2, n = 34) 4-months later. Half of the participants received the TSST in the early, the other half in the late afternoon. Discontinuous growth models were applied to model three phases of the stress response (preTSST, reactivity, recovery) for each marker. Subsequently, the stability of these phases was analyzed. Stability and test-retest reliability of standard physiological stress markers such as Area-under-the-Curve (AUCG, AUCI), Absolute Peak Change, and Relative Peak Change (RPC) were analyzed as well. We did not observe strong test-retest effects in any of the endocrinological measures. In contrast, test-retest effects in subjective stress were characterized by a faster drop directly after the second TSST, whereas the initial increase before the test period was the same for both test-days. Regarding test-retest-reliability, AUCG was the most reliable measure across all endocrinological and subjective stress markers (range: r = .606 to .858), while AUCI and RPC (range: r = - .146 to .548) were least reliable. A 4-month interval is a sufficient time interval between two repeated TSST exposures to largely reinstate the physiological stress response, which was also true for the initial psychological stress response. Thus, the TSST is well applicable in longitudinal studies.

Neurotrophic Factor Levels in Preterm Infants: A Systematic Review and Meta-Analysis.

Objectives: Through a systematic review and meta-analysis of the literature we aimed to compare the levels of BDNF, NGF, NT-3, NT-4, and GDNF between human term and preterm infants, and investigate factors implicated in the variability of effect size estimates. Methods: The analysis was performed in three online databases, MEDLINE Complete, PsycINFO, and CINAHL. A random effects model was used to calculate the standardized mean difference (SMD) of neurotrophic factor levels in preterm infants vs. term within a 95% confidence interval (CI). To explore sources of heterogeneity meta-regression models were implemented. Results: Sixteen studies were included in this meta-analysis. A combined sample of 1,379 preterm and 1,286 term newborns were evaluated. We identified significant lower BDNF (SMD = -0.32; 95% CI: -0.59, -0.06; p = 0.014) and NT-3 (SMD = -0.31; 95% CI: -0.52, -0.09; p = 0.004) levels in preterm compared to term infants. No significant difference was observed in NGF and NT-4 levels between groups. Given that only two effect sizes were generated for GDNF levels, no meta-analytical model was performed. Meta-regression models revealed sample type (placental tissue, cerebrospinal fluid, peripheral blood, and umbilical cord blood) as a significant moderator of heterogeneity for BDNF meta-analysis. No significant associations were found for gestational week, birth weight, and clinical comorbidity of newborns with effect sizes. Conclusions: Our findings indicated that lower BDNF and NT-3 levels may be associated with preterm birth. Future studies with larger samples sizes should investigate neurodevelopmental manifestations resulting from neurotrophic factor dysregulation among preterm infants.

White matter deficits in cocaine use disorder: convergent evidence from in vivo diffusion tensor imaging and ex vivo proteomic analysis.

White matter (WM) abnormalities in patients with cocaine use disorder (CUD) have been studied; however, the reported effects on the human brain are heterogenous and most results have been obtained from male participants. In addition, biological data supporting the imaging findings and revealing possible mechanisms underlying the neurotoxic effects of chronic cocaine use (CU) on WM are largely restricted to animal studies. To evaluate the neurotoxic effects of CU in the WM, we performed an in vivo diffusion tensor imaging assessment of male and female cocaine users (n = 75) and healthy controls (HC) (n = 58). Moreover, we performed an ex vivo large-scale proteomic analysis using liquid chromatography-tandem mass spectrometry in postmortem brains of patients with CUD (n = 8) and HC (n = 12). Compared with the HC, the CUD group showed significant reductions in global fractional anisotropy (FA) (p < 0.001), and an increase in global mean (MD) and radial diffusion (RD) (both p < 0.001). The results revealed that FA, RD, and MD alterations in the CUD group were widespread along the major WM tracts, after analysis using the tract-based special statistics approach. Global FA was negatively associated with years of CU (p = 0.0421) and female sex (p < 0.001), but not with years of alcohol or nicotine use. Concerning the fibers connecting the left to the right prefrontal cortex, Brodmann area 9 (BA9), the CUD group presented lower FA (p = 0.006) and higher RD (p < 0.001) values compared with the HC group. A negative association between the duration of CU in life and FA values in this tract was also observed (p = 0.019). Proteomics analyses in BA9 found 11 proteins differentially expressed between cocaine users and controls. Among these, were proteins related to myelination and neuroinflammation. In summary, we demonstrate convergent evidence from in vivo diffusion tensor imaging and ex vivo proteomics analysis of WM disruption in CUD.

A behavioral economic risk aversion experiment in the context of the COVID-19 pandemic.

We investigated what degree of risk of infection with COVID-19 is necessary so that people intend to stay home, even when doing so means losing their salary. We conducted an online survey across Brazil during the initial outbreak, in which 8,345 participants answered a questionnaire designed to identify the maximum tolerated risk (k') necessary for them to disregard social distancing recommendations and guarantee their salaries. Generalized linear mixed models, path analysis structural equation, and conditional interference classification tree were performed to further understand how sociodemographic factors impact k' and to establish a predictive model for the risk behavior of leaving home during the pandemic. We found that, on average, people tolerate 38% risk of infection to leave home and earn a full salary, but this number decreased to 13% when the individual risk perception of becoming ill from severe acute respiratory syndrome coronavirus-2 is considered. Furthermore, participants who have a medium-to-high household income and who are older than 35 years are more likely to be part of the risk-taking group who leave home regardless of the potential COVID-19 infection level; while participants over 45 years old and with good financial health are more likely to be part of the risk-averse group, who stay home at the expense of any salary offered. Our findings add to the political and public debate concerning lockdown strategies by showing that, contrary to supposition, people with low socioeconomic status are not more likely to ignore social distancing recommendations due to personal economic matters.