Seven robust and easy to obtain biomarkers to measure acute stress.

With the purpose of identifying a sensitive, robust, and easy-to-measure set of biomarkers to assess stress reactivity, we here study a large set of relatively easy to obtain markers reflecting subjective, autonomic nervous system (ANS), endocrine, and inflammatory responses to acute social stress (n = 101). A subset of the participants was exposed to another social stressor the next day (n = 48) while being measured in the same way. Acute social stress was induced following standardized procedures. The markers investigated were self-reported positive and negative affect, heart rate, electrodermal activity, salivary cortisol, and ten inflammatory markers both in capillary plasma and salivary samples, including IL-22 which has not been studied in response to acute stress in humans before. Robust effects (significant effect in the same direction for both days) were found for self-reported negative affect, heart rate, electrodermal activity, plasma IL-5, plasma IL-22, salivary IL-8 and salivary IL-10. Of these seven markers, the participants' IL-22 responses on the first day were positively correlated to those on the second day. We found no correlations between salivary and capillary plasma stress responses for any of the ten cytokines and somewhat unexpectedly, cytokine responses in saliva seemed more pronounced and more in line with previous literature than cytokines in capillary plasma. In sum, seven robust and easy to obtain biomarkers to measure acute stress response were identified and should be used in future stress research to detect and examine stress reactivity. This includes IL-22 in plasma as a promising novel marker.

Detection of arousal and valence from facial expressions and physiological responses evoked by different types of stressors.

Automatically detecting mental state such as stress from video images of the face could support evaluating stress responses in applicants for high risk jobs or contribute to timely stress detection in challenging operational settings (e.g., aircrew, command center operators). Challenges in automatically estimating mental state include the generalization of models across contexts and across participants. We here aim to create robust models by training them using data from different contexts and including physiological features. Fifty-one participants were exposed to different types of stressors (cognitive, social evaluative and startle) and baseline variants of the stressors. Video, electrocardiogram (ECG), electrodermal activity (EDA) and self-reports (arousal and valence) were recorded. Logistic regression models aimed to classify between high and low arousal and valence across participants, where "high" and "low" were defined relative to the center of the rating scale. Accuracy scores of different models were evaluated: models trained and tested within a specific context (either a baseline or stressor variant of a task), intermediate context (baseline and stressor variant of a task), or general context (all conditions together). Furthermore, for these different model variants, only the video data was included, only the physiological data, or both video and physiological data. We found that all (video, physiological and video-physio) models could successfully distinguish between high- and low-rated arousal and valence, though performance tended to be better for (1) arousal than valence, (2) specific context than intermediate and general contexts, (3) video-physio data than video or physiological data alone. Automatic feature selection resulted in inclusion of 3-20 features, where the models based on video-physio data usually included features from video, ECG and EDA. Still, performance of video-only models approached the performance of video-physio models. Arousal and valence ratings by three experienced human observers scores based on part of the video data did not match with self-reports. In sum, we showed that it is possible to automatically monitor arousal and valence even in relatively general contexts and better than humans can (in the given circumstances), and that non-contact video images of faces capture an important part of the information, which has practical advantages.

Understanding the combined effects of sleep deprivation and acute social stress on cognitive performance using a comprehensive approach.

Background: Sleep deprivation (SD) and acute social stress are common, often unavoidable, and frequently co-occurring stressors in high-risk professions. Both stressors are known to acutely induce inflammatory responses and an increasing body of literature suggests this may lead to cognitive impairment. This study examined the combined effects of total SD and acute social stress on cognitive performance and took a comprehensive approach to explore their (shared) underlying mechanism leading to cognitive decline. Method: We recorded cognitive performance on a response inhibition task and a multitask and monitored a range of inflammatory, psychophysiological and self-reported markers in 101 participants, both before and after one night of either sleep (control group: N = 48) or SD (N = 53), and both before and after a social stressor (Trier Social Stress Test). Results: SD decreased cognitive performance. The social stress test also results in cognitive performance decline in the control group on the response inhibition task, but improved rather than decreased performance of sleep deprived participants on both tasks. The subjective ratings of mental effort also reflect this antagonistic interaction, indicating that the social stressor when sleep-deprived also reduced mental effort. In the inflammatory and physiological measures, this pattern was only reflected by IL-22 in blood. SD reduced blood IL-22 concentrations, and the social stress reduced IL-22 in the control group as well, but not in sleep-deprived participants. There were no interactive effects of SD and social stress on any other inflammatory or psychophysiological measures. The effects of the social stress test on autonomic measures and subjective results suggest that increased arousal may have benefited sleep-deprived participants' cognitive performance. Discussion: SD generally decreased cognitive performance and increased required mental effort. By contrast, the isolated effects of a social stressor were not generic, showing a positive effect on cognitive performance when sleep deprived. Our study is the first that studied combined effects of sleep deprivation and acute social stress on cognitive performance and inflammatory markers. It provides a comprehensive overview of effects of these stressors on a range of variables. We did not show unequivocal evidence of an underlying physiological mechanism explaining changes in performance due to (the combination of) sleep deprivation and social stress, but consider IL-22 as a possible cytokine involved in this mechanism and certainly worth following up on in future research.

Predictors of the Acceptance of an Electronic Coach Targeting Self-management of Patients With Type 2 Diabetes: Web-Based Survey.

BACKGROUND: Type 2 diabetes (T2D) is a lifestyle-related disease whose prevalence increases with age. Diabetes self-management through mobile health (mHealth) apps enables patients with T2D to improve their health. According to the Technology Acceptance Model (TAM), technology acceptance (ie, intended use) is necessary to ensure mHealth can be implemented successfully. Therefore, the specific acceptance requirements of patients with T2D should be considered. OBJECTIVE: This cross-sectional study aims to examine the extent to which different TAM predictors are associated with the acceptance of a diabetes app including an electronic coach (eCoach; Iris app) among patients with T2D. METHODS: Using a web-based survey, data on 92 patients with T2D (mean age 62.76 years, SD 8.29 years) were collected. Acceptance of the Iris app with the TAM predictors (ie, perceived usefulness, perceived ease of use, social influence, perceived self-efficacy, perceived security, prior usage experience, perceived health, and propensity of data/information sharing) was assessed. Further, control variables (ie, gender, age, education, ethnicity, household, BMI, amount of years with diabetes, diabetes-related complaints, and medication use) were assessed. RESULTS: Multiple linear regression analyses showed that acceptance of the Iris app was positively associated with perceived usefulness (ß=.57, P<.001), social influence (subjective norm; ß=.20, P=.004), and willingness to share data (ß=.25, P<.001). In addition, acceptance regarding the Iris app was higher among patients with T2D with overweight (ß=.23, P=.01) or obese BMI (ß=.21, P=.01). The model explained 75.8% of the variance in the acceptance of the Iris app by patients with T2D. In addition, perceived usefulness of the Iris app was positively related to perceived ease of use (ß=.32, P<.001), subjective norm (ß=.26, P=.004), perceived control (ß=.19, P=.03), willingness to share data (ß=.20, P=.01) regarding the Iris app, and perceived security regarding general use of apps/smartphone/internet (ß=.15, P=.04). The model explained 58.2% of the variance in patients' perceived usefulness about the Iris app. CONCLUSIONS: Among patients with T2D, the belief that the use of the Iris app is helpful/beneficial, the willingness to share their Iris app data, and others' approval of using this app can stimulate the acceptance of this app. In addition, the belief that the use of (health) apps is reliable and secure, the belief that the use of the Iris app is easy to use, a higher perceived capability and personal control with using this app, the willingness to share their Iris app data, and others' approval of using this app can stimulate the perceived usefulness of such an app. These TAM predictors explained a high variance in acceptance and perceived usefulness of the Iris app. Implications for practice are addressed.

Harmful Drinking Phenotype in a Large Dutch Community Sample.

AIMS: Harmful drinking patterns are shaped by a broad complex interaction of factors, societal and individual, psychological and behavioral. Although previous studies have focused on a few variables at a time, the current study simultaneously examines a large number of variables in order to create a comprehensive view (i.e. phenotype) of harmful drinking, and to rank the main predictors of harmful and non-harmful drinking by order of importance. METHODS: We surveyed a large sample of Dutch adults about their habitual drinking characteristics and attitudes, perceptions and motives for drinking. We fed 45 variables into a random forest machine learning model to identify predictors for (1) drinking within and in excess of Dutch guideline recommendations and (2) harmful and non-harmful drinking. RESULTS: In both models, respondents' subjective perceptions of 'responsible drinking', both per occasion and per week, showed the strongest predictive potential for different drinking phenotypes. The next strongest factors were respondents' reason for drinking, motives for drinking and age. Other variables, such as drinking location, knowledge about alcohol-related health risks and consumption of different beverage types, were not strong predictors of drinking phenotypes. CONCLUSIONS: Although the direction of the relationship is unclear from the findings, they suggest that interventions and policy measures aimed at individuals and social norms around drinking may offer promise for reducing harmful drinking. Messaging and promotion of drinking guidelines should be tailored with this in mind.

A high-fibre personalised dietary advice given via a web tool reduces constipation complaints in adults.

Constipation can greatly impact the quality of life (QoL), which can be relieved by dietary fibres; however, preserving a higher fibre intake remains a challenge. We investigated the effects of a personalised dietary advice (PDA) on fibre intake and mild constipation complaints. A total number of twenty-five adults with mild constipation complaints were included in a 4-week observation period followed by a 4-week personalised intervention. The PDA provided high-fibre alternatives via a web tool. In weeks 1, 4 and 8, dietary intake, constipation complaints and QoL were assessed. Furthermore, participants collected a faecal sample at weeks 1, 4 and 8 to determine microbiota diversity and composition, and short-chain fatty acids (SCFA). Participants completed questions daily for 8 weeks regarding abdominal complaints, stool frequency and stool consistency. Fibre intake in week 8 was significantly higher compared to week 1 (Δ = 5·7 ± 6·7 g, P < 0·001) and week 4 (Δ = 5·2 ± 6·4 g, P < 0·001). Constipation severity and QoL significantly improved at week 8 compared to the observation period (P < 0·001). A higher fibre intake significantly reduced constipation severity (ß = -0·031 (-0·05; -0·01), P = 0·001) and the QoL (ß = -0·022 (-0·04; -0·01), P = 0·009). Stool consistency (P = 0·040) and abdominal pain (P = 0·030) improved significantly during the intervention period (P = 0·040), but stool frequency did not. Average microbial alpha diversity and composition and SCFA concentrations did not change over time, but indicated individual-specific dynamics. Several SCFAs were associated with constipation complaints. To conclude, a PDA effectively increased fibre intake and subsequently reduced constipation complaints, indicating that guided dietary adjustments are important and feasible in the treatment of mild constipation complaints.

Increasing dietary fibre intake in healthy adults using personalised dietary advice compared with general advice: a single-blind randomised controlled trial.

OBJECTIVE: A high-fibre diet is associated with a lower risk for diseases. However, few adults meet the dietary fibre recommendation. Therefore, the effects and acceptance of an algorithm-generated personalised dietary advice (PDA) compared with general advice (GA) on fibre intake were investigated. DESIGN: A 6-week, single-blind randomised controlled trial with a 3-month follow-up. SETTING: PDA was based on habitual intake and provided fibre-rich alternatives using a website; GA contained brochures. Dietary intake was assessed at baseline, week 1, week 6 and 3-month follow-up. Both groups evaluated their advice at week 6. All participants had access to PDA from week 7 until 3-month follow-up. PARTICIPANTS: Two groups of healthy adults: PDA (n 34) and GA (n 47). For 3-month follow-up analysis, participants were re-divided into visitors (n 52) and non-visitors (n 26) of the PDA. RESULTS: At week 6, energy intake remained stable in both groups, but fibre intake per 1000 kcal increased non-significantly in both groups (PDA = Δ0·5 ± 2·8; GA = Δ0·8 ± 3·1, P = 0·128). Importantly, a significantly higher percentage of PDA participants adhered to the recommendation compared with week 1 (PDA = 21 % increase; GA = 4 % increase, P ≤ 0·001). PDA participants evaluated the advice significantly better compared with GA participants. At 3-month follow-up, fibre intake increased compared with baseline (visitors = Δ2·2 ± 2·6, P < 0·001; non-visitors = Δ1·5 ± 1·9, P = 0·001), but was insignificantly different between groups. Visitors had a decrease and non-visitors had an increase in energy intake (visitors =Δ - 132 ± 525; non-visitors = Δ109 ± 507, P = 0·055). CONCLUSIONS: The algorithm-generated PDA was well accepted and stimulated adherence to the recommendations more than GA, indicating to be a suitable and cost-efficient method for improving dietary fibre intake in healthy adults.

Alcohol Consumption, Drinking Patterns, and Cognitive Performance in Young Adults: A Cross-Sectional and Longitudinal Analysis.

Long-term alcohol abuse is associated with poorer cognitive performance. However, the associations between light and moderate drinking and cognitive performance are less clear. We assessed this association via cross-sectional and longitudinal analyses in a sample of 702 Dutch students. At baseline, alcohol consumption was assessed using questionnaires and ecological momentary assessment (EMA) across four weeks ('Wave 1'). Subsequently, cognitive performance, including memory, planning, and reasoning, was assessed at home using six standard cognition tests presented through an online platform. A year later, 436 students completed the four weeks of EMA and online cognitive testing ('Wave 2'). In both waves, there was no association between alcohol consumption and cognitive performance. Further, alcohol consumption during Wave 1 was not related to cognitive performance at Wave 2. In addition, EMA-data-based drinking patterns, which varied widely between persons but were relatively consistent over time within persons, were also not associated with cognitive performance. Post-hoc analyses of cognitive performance revealed higher within-person variance scores (from Wave 1 to Wave 2) than between-person variance scores (both Wave 1 and Wave 2). In conclusion, no association was observed between alcohol consumption and cognitive performance in a large Dutch student sample. However, the online cognitive tests performed at home may not have been sensitive enough to pick up differences in cognitive performance associated with alcohol consumption.

Beneficial effect of personalized lifestyle advice compared to generic advice on wellbeing among Dutch seniors - An explorative study.

The aim of this explorative study is to evaluate whether personalized compared to generic lifestyle advice improves wellbeing in a senior population. We conducted a nine-week single-blind randomized controlled trial including 59 participants (age 67.7 ±â€¯4.8 years) from Wageningen and its surrounding areas in the Netherlands. Three times during the intervention period, participants received either personalized advice (PA), or generic advice (GA) to improve lifestyle behavior. Personalization was based on metabolic health measures and dietary intake resulting in an advice that highlighted food groups and physical activity types for which behavior change was most urgent. Before and after the intervention period self-perceived health was evaluated as parameter of wellbeing using a self-perceived health score (single-item) and two questionnaires (Vita-16 and Short Form-12). Additionally, anthropometry and physical functioning (short physical performance battery, SPPB) were assessed. Overall scores for self-perceived health did not change over time in any group. Resilience and motivation (Vita-16) slightly improved only in the PA group, whilst mental health (SF-12) and energy (Vita-16) showed slight improvement only in the GA group. SPPB scores improved over time in both the PA and GA group. PA participants also showed a reduction in body fat percentage and hip circumference, whereas these parameters increased in the GA group Our findings suggest that although no clear effects on wellbeing were found, still, at least on the short term, personalized advice may evoke health benefits in a population of seniors as compared to generic advice.

Systems biology of personalized nutrition.

Personalized nutrition is fast becoming a reality due to a number of technological, scientific, and societal developments that complement and extend current public health nutrition recommendations. Personalized nutrition tailors dietary recommendations to specific biological requirements on the basis of a person's health status and goals. The biology underpinning these recommendations is complex, and thus any recommendations must account for multiple biological processes and subprocesses occurring in various tissues and must be formed with an appreciation for how these processes interact with dietary nutrients and environmental factors. Therefore, a systems biology-based approach that considers the most relevant interacting biological mechanisms is necessary to formulate the best recommendations to help people meet their wellness goals. Here, the concept of "systems flexibility" is introduced to personalized nutrition biology. Systems flexibility allows the real-time evaluation of metabolism and other processes that maintain homeostasis following an environmental challenge, thereby enabling the formulation of personalized recommendations. Examples in the area of macro- and micronutrients are reviewed. Genetic variations and performance goals are integrated into this systems approach to provide a strategy for a balanced evaluation and an introduction to personalized nutrition. Finally, modeling approaches that combine personalized diagnosis and nutritional intervention into practice are reviewed.

The effects of acute tryptophan depletion on speech and behavioural mimicry in individuals at familial risk for depression.

Major depressive disorder (MDD) has been associated with abnormalities in speech and behavioural mimicry. These abnormalities may contribute to the impairments in interpersonal functioning that are often seen in MDD patients. MDD has also been associated with disturbances in the brain serotonin system, but the extent to which serotonin regulates speech and behavioural mimicry remains unclear. In a randomized, double-blind, crossover study, we induced acute tryptophan depletion (ATD) in individuals with or without a family history of MDD. Five hours afterwards, participants engaged in two behavioural-mimicry experiments in which speech and behaviour were recorded. ATD reduced the time participants waited before speaking, which might indicate increased impulsivity. However, ATD did not significantly alter speech otherwise, nor did it affect mimicry. This suggests that a brief lowering of brain serotonin has limited effects on verbal and non-verbal social behaviour. The null findings may be due to low test sensitivity, but they otherwise suggest that low serotonin has little effect on social interaction quality in never-depressed individuals. It remains possible that recovered MDD patients are more strongly affected.

Empathic accuracy and oxytocin after tryptophan depletion in adults at risk for depression.

RATIONALE: Major depressive disorder (MDD) has been associated with disturbances in social functioning and in the brain serotonin system. Reduced levels of serotonin may negatively influence social functioning, for example by impairing the recognition of facial emotion expressions. OBJECTIVES: The present study investigated the effect of acute tryptophan depletion (ATD), which reduces brain serotonin, on a related component of social functioning, empathic accuracy (EA), and oxytocin levels. METHODS: Individuals with (FH+) and without (FH−) a family history of MDD participated in a randomized, double-blind, crossover study. On two separate test days, participants ingested tryptophan-deficient and nutritionally balanced amino acid mixtures. Six hours later, they performed an EA task, which involved watching videos of people recounting autobiographical emotional events. While watching, participants continuously rated how these people felt during the recounting. Mood state was repeatedly assessed using the Positive Affect and Negative Affect Schedule and a series of visual analogue scales. Blood samples obtained at baseline and 5 h after mixture ingestion were assessed for tryptophan and oxytocin levels. RESULTS: ATD decreased circulating levels of tryptophan and oxytocin. Nevertheless, there were no significant effects of ATD on EA or mood in either FH group. CONCLUSIONS: While previous studies have shown that acute reductions in brain serotonin alter the recognition of facial emotion expressions in never-depressed individuals, the present study suggests that empathic abilities may remain unaffected.

The Effects of Tryptophan on Everyday Interpersonal Encounters and Social Cognitions in Individuals with a Family History of Depression.

BACKGROUND: Individuals with a family history of depression show subtle abnormalities in the processing of social stimuli. This could negatively affect their interpersonal functioning and contribute to their depression risk. Repeated administration of the serotonin precursor tryptophan has previously been shown to increase agreeable behavior and reduce quarrelsome behavior in irritable people, who are also considered at risk for depression. METHODS: To examine the effects of tryptophan on social functioning in individuals with a family history of depression, 40 men and women with at least one first-degree relative with depression received tryptophan (1g three times a day) and placebo for 14 days each in a double-blind crossover design and recorded their social behavior and mood during everyday interpersonal encounters. Participants also provided daily ratings of their positive and negative cognitions concerning their social functioning. RESULTS: Tryptophan improved mood. Unexpectedly, tryptophan increased quarrelsome behavior and reduced agreeable behavior, specifically during interactions at home. The behavioral effects of tryptophan were not moderated by mood or by the interaction partner. Negative social cognitions were lower when tryptophan was given second and lower during placebo when placebo was given second. CONCLUSION: Overall, tryptophan may not alter social behavior in individuals with a family history of depression as it does in irritable people. However, the behavioral effects of tryptophan at home might be seen as a way for individuals with a family history of depression to achieve more control. Over time, this may positively influence the way they feel and think about themselves in a social context.

Studying the neurobiology of human social interaction: Making the case for ecological validity.

With this commentary we make the case for an increased focus on the ecological validity of the measures used to assess aspects of human social functioning. Impairments in social functioning are seen in many types of psychopathology, negatively affecting the lives of psychiatric patients and those around them. Yet the neurobiology underlying abnormal social interaction remains unclear. As an example of human social neuroscience research with relevance to biological psychiatry and clinical psychopharmacology, this commentary discusses published experimental studies involving manipulation of the human brain serotonin system that included assessments of social behavior. To date, these studies have mostly been laboratory-based and included computer tasks, observations by others, or single-administration self-report measures. Most laboratory measures used so far inform about the role of serotonin in aspects of social interaction, but the relevance for real-life interaction is often unclear. Few studies have used naturalistic assessments in real life. We suggest several laboratory methods with high ecological validity as well as ecological momentary assessment, which involves intensive repeated measures in naturalistic settings. In sum, this commentary intends to stimulate experimental research on the neurobiology of human social interaction as it occurs in real life.

The influence of affective empathy and autism spectrum traits on empathic accuracy.

Autism spectrum disorder is characterized by interpersonal deficits and has been associated with limited cognitive empathy, which includes perspective taking, theory of mind, and empathic accuracy (EA). The capacity for affective empathy may also be impaired. In the present study we aimed to determine if EA in normally developing individuals with varying levels of autism spectrum traits is moderated by trait affective empathy. Fifty male and fifty female participants ('perceivers') completed the Autism-Spectrum Quotient and the Balanced Emotional Empathy Scale to assess autism spectrum traits and trait affective empathy, respectively. EA was assessed using a Dutch-language version of a previously developed task and involved rating the feelings of others ('targets') verbally recounting autobiographical emotional events. Targets varied in trait emotional expressivity, assessed using the Berkeley Expressivity Questionnaire. Perceivers with more autism spectrum traits performed worse on the EA task, particularly when their trait affective empathy was relatively low. Interpersonal deficits in autism spectrum disorder may be partially explained by low cognitive empathy. Further, they might be aggravated by a limited capacity for affective empathy.

Communal and agentic behaviour in response to facial emotion expressions.

Facial emotions are important for human communication. Unfortunately, traditional facial emotion recognition tasks do not inform about how respondents might behave towards others expressing certain emotions. Approach-avoidance tasks do measure behaviour, but only on one dimension. In this study 81 participants completed a novel Facial Emotion Response Task. Images displaying individuals with emotional expressions were presented in random order. Participants simultaneously indicated how communal (quarrelsome vs. agreeable) and how agentic (dominant vs. submissive) they would be in response to each expression. We found that participants responded differently to happy, angry, fearful, and sad expressions in terms of both dimensions of behaviour. Higher levels of negative affect were associated with less agreeable responses specifically towards happy and sad expressions. The Facial Emotion Response Task might complement existing facial emotion recognition and approach-avoidance tasks.

Comparability of the Social Behavior Inventory in English and Dutch.

The Social Behavior Inventory (SBI) assesses social behaviors along the 2 orthogonal axes defining the interpersonal circumplex; that is, in terms of quarrelsomeness-agreeableness and dominance-submissiveness. To contribute to evidence evaluating the cross-cultural construct validity of the SBI, we investigated whether there are differences in how English-speaking students living in Canada and Dutch-speaking students living in The Netherlands view the SBI items. Results suggested there is similarity in the meaning of the items in the 2 cultures. The location of the original English SBI items on the 2 axes of the interpersonal circumplex was generally as expected. Similar results were found for a Dutch translation of the SBI. Differences occurred primarily along the dominance-submissiveness axis and could be explained by cultural differences in men's focus on power.

Mood disorders in everyday life: a systematic review of experience sampling and ecological momentary assessment studies.

In the past two decades, the study of mood disorder patients using experience sampling methods (ESM) and ecological momentary assessment (EMA) has yielded important findings. In patients with major depressive disorder (MDD), the dynamics of their everyday mood have been associated with various aspects of their lives. To some degree similar studies have been conducted in patients with bipolar disorder (BD). In this paper we present the results of a systematic review of all ESM/EMA studies in MDD and BD to date. We focus not only on the correlates of patients' everyday mood but also on the impact on treatment, residual symptoms in remitted patients, on findings in pediatric populations, on MDD/BD specificity, and on links with neuroscience. After reviewing these six topics, we highlight the benefits of ESM/EMA for researchers, clinicians, and patients, and offer suggestions for future studies.

Social defeat stress in rats: escalation of cocaine and "speedball" binge self-administration, but not heroin.

RATIONALE: Exposure to intermittent episodes of social defeat stress can increase drug seeking and leads to intense drug taking in rats. OBJECTIVES: This study investigated the consequences of repeated, intermittent social defeat stress on patterns of drug self-administration in rats with access to heroin, cocaine, or a heroin-cocaine combination ("speedball"). METHODS: Male Long-Evans rats were either handled (controls) or subjected to 25-min social defeat stress episodes on days 1, 4, 7, and 10 during confrontations with an aggressive resident. Ten days following the last defeat, rats were assessed for locomotor cross-sensitization in response to heroin or cocaine. Animals were then prepared with intrajugular catheters for drug self-administration. Separate groups of controls and defeated rats were examined for self-administration of heroin (experiment 1), a heroin-cocaine combination (experiment 2), or cocaine (experiment 3). Drug self-administration patterns were evaluated using fixed or progressive ratio schedules of reinforcement during limited access sessions or a 24-h unlimited access binge. RESULTS: Rats with a history of intermittent social defeat stress showed sensitized locomotor behavior when challenged with heroin or cocaine relative to controls. During the 24-h binge session, defeated rats escalated cocaine-taking behavior (ca. 110 mg/kg vs. 66 mg/kg in controls), persisted in self-administering cocaine or the heroin-cocaine mixture for more hours, and showed a tendency for increased heroin-cocaine intake, but no effects on heroin taking. CONCLUSIONS: A history of social defeat stress seems to preferentially promote escalated intake of cocaine but not heroin, unless a heroin-cocaine combination is available.