10 results
93132 Relationship between Level of Response to Alcohol and Body Weight Status in Individuals across the Spectrum of Alcohol Use and Misuse
- Rhianna R. Vergeer, Bethany L. Stangl, Melanie L. Schwandt, Nancy Diazgranados, Vijay A. Ramchandani
-
- Journal:
- Journal of Clinical and Translational Science / Volume 5 / Issue s1 / March 2021
- Published online by Cambridge University Press:
- 30 March 2021, p. 137
-
- Article
-
- You have access Access
- Open access
- Export citation
-
ABSTRACT IMPACT: Improved understanding of the relationship between level of response to alcohol and body weight in the context of other contributing factors will help inform prevention and intervention efforts regarding obesity. OBJECTIVES/GOALS: We evaluated the association between level of response to alcohol and weight status across the spectrum of alcohol misuse. We hypothesized that lower level of response to alcohol would be associated with heavier weight, after controlling for obesity risk factors like food addiction, impulsivity, and low socioeconomic status. METHODS/STUDY POPULATION: Adult participants (N=587) enrolled in NIAAA’s natural history study completed Self-Rating of the Effects of Alcohol (SRE), a retrospective measure of level of response to alcohol, along with Lifetime Drinking History (LDH); Yale Food Addiction (FA) Scale; Barratt Impulsiveness Scale (BIS); Delayed Discounting Task (DDT). Structured Clinical Interviews for DSM disorders were conducted to identify individuals with current alcohol use disorder (AUD). Body mass index (BMI), computed from height and weight measured during the study, and used to stratify participants into 3 groups: normal weight (N=222), overweight (N=219), or obese (N=146). RESULTS/ANTICIPATED RESULTS: SRE scores during heaviest drinking period were lowest in the heavier weight group, after accounting for FA, impulsivity, alcohol-related, and demographic variables (ê•2=238.5, p=0.002, Cox and Snell Pseudo R2=0.43). Compared to the obese group, normal weight and overweight groups had fewer FA symptoms and higher BIS cognitive complexity (p values<0.01) but similar rates of current AUD. Relative to the obese group, the normal weight group was more likely to be White, and to have lower household incomes but more education, more years of heavy drinking (LDH), and steeper delayed discounting, p values ≤0.03. The overweight group had a higher proportion of males than did the obese group, p<0.001. DISCUSSION/SIGNIFICANCE OF FINDINGS: Lower level of response during heaviest drinking period was significantly associated with current weight status, suggesting a relationship between alcohol sensitivity and BMI. Future work will explore pharmacokinetic-pharmacodynamic and additional risk factors underlying this relationship.
4491 Cumulative Childhood Trauma Load Across Race in Individuals with Alcohol Use Disorder
- Nia Byrd, Bethany L. Stangl, Melanie L. Schwandt, Nancy Diazgranados, Vijay A. Ramchandani
-
- Journal:
- Journal of Clinical and Translational Science / Volume 4 / Issue s1 / June 2020
- Published online by Cambridge University Press:
- 29 July 2020, pp. 26-27
-
- Article
-
- You have access Access
- Open access
- Export citation
-
OBJECTIVES/GOALS: Our objective was to investigate racial differences in experiencing multiple categories of childhood trauma (CT) and the differential impact on alcohol use in individuals with alcohol use disorder (AUD). We hypothesized that there would be a differential additive effect of CT categories endorsed and drinking behaviors between racial groups. METHODS/STUDY POPULATION: Participants were recruited through the NIAAA screening protocol where they completed alcohol-related assessments including a 90-day Timeline Followback (TLFB) and the Alcohol Use Disorder Identification Test (AUDIT). Structured Clinical Interviews for DSM disorders were conducted to identify participants with lifetime alcohol dependence (DSM-IV) or AUD (DSM-5) (N = 1152). Participants self-identified as Black or White completed the Childhood Trauma Questionnaire (CTQ) which assesses 5 types of CT: emotional abuse, physical abuse, sexual abuse, physical neglect, and emotional neglect, and were classified into 3 CT groups: no trauma, 1 type of trauma, and 2+ types of trauma endorsed. RESULTS/ANTICIPATED RESULTS: For Black participants (N = 583), 21.6% experienced no trauma, 21% experienced 1 type, and 57.4% experienced 2 or more types, with the most common being physical abuse and emotional neglect. For White participants (N = 569), 32.1% experienced no trauma, 20.6% experienced 1 type, and 47.3% experienced 2 or more types, with the most common being emotional neglect and emotional abuse. There were significant associations between CT groups, TLFB, and AUDIT measures. For Black participants, AUDIT-Harm and AUDIT Total were significantly different across the 3 CT groups (all p values <0.05). For White participants, Heavy Drinking Days was significantly different across the 3 CT groups (p = 0.028), with trends for AUDIT-Harm (p = 0.061) and AUDIT-Dependence (p<0.065). DISCUSSION/SIGNIFICANCE OF IMPACT: In individuals with AUD, there were significant positive associations between the number of CT categories endorsed and alcohol use across race, suggesting a cumulative effect of CT on risky alcohol use. Future work includes exploring personality and behavioral mediators of the relationship between cumulative trauma load and drinking.
4288 Identifying Predictive Variables of High-Intensity Binge Drinking Through the Use of a Machine Learning Algorithm
- James Keoni Morris, Josh L. Gowin, Melanie L. Schwandt, Nancy Diazgranados, Vijay A. Ramchandani
-
- Journal:
- Journal of Clinical and Translational Science / Volume 4 / Issue s1 / June 2020
- Published online by Cambridge University Press:
- 29 July 2020, p. 135
-
- Article
-
- You have access Access
- Open access
- Export citation
-
OBJECTIVES/GOALS: To test if a machine learning algorithm could predict a person’s capacity to binge drink and explore what measures might be important for identifying individuals at risk for high-intensity binge drinking behaviors. METHODS/STUDY POPULATION: The sample included 1177 (474 female) non-treatment-seeking drinkers (age: 18-91 years), that were assigned to a group based on their heaviest drinking day reported in a 90-Day Alcohol Timeline Followback questionnaire. The groups were Non-Bingers (female: 12 drinks, male:>15 drinks). The sample was divided into a training sample (N = 884) and a testing sample (N = 293). A machine learning algorithm called random forest was then used to generate a predictive model based on measures of substance use, personality traits, and trauma. The model was applied to the testing sample to determine accuracy. RESULTS/ANTICIPATED RESULTS: The first model correctly assigned 190 out of 293 subjects, giving it a total error rate of 0.35, with lowest rates for non-binge (0.19) and high-intensity (0.18), while medium-intensity had the highest error rate (0.86). The most important variables for the accuracy of the model included: total score on the Alcohol Use Disorder Identification Test, first five sub-score of the Self-Reported Effects of Alcohol, Compulsive Drinking subscale, and presence of a current psychiatric diagnosis. As a follow-up analysis, we built and tested another random forest model without the use of drinking dependence measures. This model had a total error rate of 0.39, and introduced other important variables such as smoking behaviors, perceived stress, IQ, and number of negative life events. DISCUSSION/SIGNIFICANCE OF IMPACT: Our study showed that it was possible for a machine learning algorithm to predict binge drinking intensity better than chance. Drinking patterns were the most robust predictors, and stress, IQ, and psychiatric diagnoses were also useful in predicting binge drinking intensity.
4191 The Role of Suggestibility and Trait Anxiety in Young Adult Alcohol Use
- Alexandra Cowand, Melanie Schwandt, Alyssa Schneider, Jodi M. Gilman, Nancy Diazgranados, Vijay A. Ramchandani, Bethany L. Stangl
-
- Journal:
- Journal of Clinical and Translational Science / Volume 4 / Issue s1 / June 2020
- Published online by Cambridge University Press:
- 29 July 2020, p. 149
-
- Article
-
- You have access Access
- Open access
- Export citation
-
OBJECTIVES/GOALS: The purpose of this study was to investigate how suggestibility and social susceptibility relate to alcohol use in young adult non-dependent alcohol users, and the role of trait anxiety in this relationship. We hypothesized that greater trait anxiety would be associated with higher levels of alcohol misuse, and this would be mediated by suggestibility. METHODS/STUDY POPULATION: Study participants enrolled in the NIAAA screening and assessment protocol completed questionnaires on suggestibility, anxiety, and alcohol use. The Multidimensional Iowa Suggestibility Scale (MISS) is a 95-question self-report assessment of suggestibility. Trait anxiety is assessed with the State Trait Anxiety Inventory-Trait (STAI-T). Alcohol measures included the Alcohol Use Disorder Identification Test (AUDIT). Structured Clinical Interviews for DSM-IV or DSM-5 disorders were conducted, and non-dependent participants (N = 113) were considered. A median split was conducted (median age = 35.1 years), with the focus of this study on the younger individuals (N = 55). RESULTS/ANTICIPATED RESULTS: Initial analyses showed that suggestibility, alcohol misuse, and trait anxiety all had significant positive correlations with one another. To better understand the relationship of peer influence, specifically, with drinking and anxiety, MISS subscale of Peer Conformity was analyzed. MISS total score and Peer Conformity were positively correlated with AUDIT Total as well as STAI-T Score. STAI-T Score was additionally positively correlated with AUDIT Total (all p2 = 0.222). We also looked at Peer Conformity in place of MISS Total (R2 = 0.213). In both models, only suggestibility measures were significant predictors of harmful alcohol use (p<0.01). DISCUSSION/SIGNIFICANCE OF IMPACT: In young social drinkers, there were significant positive associations between suggestibility, risky alcohol use, and trait anxiety. These results suggest that suggestibility may be a modifiable risk factor for risky alcohol consumption. Future directions include using mediation models to explore the associations between suggestibility, anxiety, and alcohol misuse.
3255 Association between dopaminergic genetic variants, COMTrs4680 and DRD2rs1076560, and alcohol consumption and reward behaviors in non-dependent drinkers
- Nancy Elizabeth Ortega, Bethany L. Stangl, Soundarya Soundararajan, Shaliciana Burrell, Hui Sun, Melanie L. Schwandt, Vijay A. Ramchandani
-
- Journal:
- Journal of Clinical and Translational Science / Volume 3 / Issue s1 / March 2019
- Published online by Cambridge University Press:
- 26 March 2019, pp. 138-139
-
- Article
-
- You have access Access
- Open access
- Export citation
-
OBJECTIVES/SPECIFIC AIMS: The objective of this exploratory study is to evaluate the relationship between the individual genetic variants in COMTrs4680 and DRDrs1076560 and relevant alcohol use behaviors (i.e. alcohol consumption and reward processing behaviors) in non-dependent drinkers within experimentally controlled IV-ASA CAIS sessions. The overall goal of this study is to begin gathering data on the influence of individual genetic variants on alcohol consumption and other drinking-related behaviors. This will aid in the creation of a polygenic model of risk for AUD which will provide more insight into how the mesolimbic pathway is affected by alcohol use. METHODS/STUDY POPULATION: Study population: The sample included male and female non-dependent drinkers (N=149). Genotypes for functional polymorphisms in COMT (rs4680) and DRD2 (rs1076560) genes were determined for all subjects from blood samples obtained during screening. Alcohol consumption was assessed using the 90-day Timeline Followback Interviews (TLFB). Study population demographics: Self-reported gender (53.5% identified as male); Self-reported race (61.2% identified as white); Age ranged from 21-46 years old, with 22 years being the mode. Experiment: Free access (open-bar) intravenous alcohol self-administration (IV-ASA) using the computer-assisted alcohol infusion system (CAIS) paradigm; Subjects had the choice of pressing a button ad libitum for IV alcohol infusions during the session, neurobehavioral questionnaires were collected throughout the 2.5-hr alcohol infusion session. Primary outcome measures included: Total Rewards, Peak breath alcohol concentration (BrAC) achieved, and Total Ethanol consumed. Statistical Analyses: Conducted using SPSS IBM Statistics Versions 1.0.0-2482; non-dependent drinkers were organized into two groups based on their genotypes, minor allele carriers and major allele homozygotes. Outcome measures were compared between genotype groups using analysis of variance or non-parametric Mann-Whitney U-test as appropriate. RESULTS/ANTICIPATED RESULTS: -We expect the genetic makeup of the sample to be reflective of larger genome samples that are publically available (e.g. e!Ensembl) - Initial analysis for COMTrs4680 did not reveal significant effects on IV-ASA measures. Specifically, the majo DISCUSSION/SIGNIFICANCE OF IMPACT: Alcohol Use Disorder (AUD) affects millions of men and women globally. The heterogeneity within AUD individuals has made it difficult to identify biological and/or psychological factors that could be targeted for the development of treatments. By using the human laboratory model of free access IV-ASA, this study evaluated the relationship between dopaminergic genetic variants, COMTrs4680 and DRDrs1076560, and alcohol consumption in non-dependent drinkers within a controlled experimental environment. This study will begin to evaluate genetic and behavioral data that can be used to create a polygenic model of risk for AUD, which will provide more insight as to how the mesolimbic reward pathway is affected by alcohol use and contributes to risk for AUD.
3207 Relation between Dopamine Transporter (DAT1) polymorphism and subjective effects of alcohol among non-dependent drinkers
- Soundarya Soundararajan, Bethany L. Stangl, Courtney L. Vaughan, Hui Sun, Falk Lohoff, Melanie L. Schwandt, Vijay Ramchandani
-
- Journal:
- Journal of Clinical and Translational Science / Volume 3 / Issue s1 / March 2019
- Published online by Cambridge University Press:
- 26 March 2019, p. 154
-
- Article
-
- You have access Access
- Open access
- Export citation
-
OBJECTIVES/SPECIFIC AIMS: Dopamine transporter (DAT1) gene variation is associated with reward-related phenotypes including alcohol response. There is also evidence for a potential moderating role for mu-opioid receptor (OPRM1) gene variation on the relationship between DAT1 variation and alcohol response measures. We aimed at studying the interaction between the DAT1 VNTR and OPRM1 A118G polymorphisms on alcohol consumption and subjective responses among non-dependent drinkers. METHODS/STUDY POPULATION: We employed a progressive ratio (PR) paradigm of intravenous alcohol self-administration (IV-ASA) using the Computer-Assisted Infusion System (CAIS) to assess the motivation for alcohol seeking and consumption in a sample of nondependent drinkers. We used the Drug Effects Questionnaire (DEQ) and Biphasic Alcohol Effects Questionnaire (BAES) to assess subjective response. IV-ASA measures included average breath alcohol concentration (BrAC) and total ethanol infused. Peripheral blood samples were collected for genotyping. Ethics approval was obtained from the NIH Addictions Institutional Review Board. RESULTS/ANTICIPATED RESULTS: Fifty participants completed the PR IV-ASA session after informed consent. There were significant interactions between the DAT1 and OPRM1 genotypes in subjective effects of alcohol. Simple main effects analysis showed that DAT1 10a allele carriers that were also OPRM1 G allele carriers had significantly higher scores for several measures: “feel the drug effects” (F (1,46)=6.573, P = 0.014), “feel intoxicated”(F(1,46)=8.613, P = 0.005) and “feeling high” (F(1,46)=10.889, P = 0.002) in DEQ and higher sedation (F(1,46)=4.575, P = 0.038) in BAES. The genotypes statistically significantly predicted average breath alcohol (F (1,61) =3.295, p=0.044) and total ethanol infused(F(1,61)=3.632, p=0.032. DAT1 VNTR and OPRM1 A118G polymorphisms taken together accounted for 6.9 and 7.8% of variations in average breath alcohol and total ethanol infused respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: Polymorphic variations in DAT1 and OPRM1 interact with each other in determining subjective effects of alcohol in intravenous alcohol infusion assessing motivation for alcohol seeking and consumption in nondependent drinkers. These epistatic interactions in subjective effects of alcohol are salient in the context of predicting and understanding neurobiological effects of alcohol and thereby the therapeutic responses in treating alcohol use disorders.
3376 Super Bingers: Traits and Patterns Associated with High-Intensity Drinking
- James Keoni Morris, Julia E. Swan, Josh L. Gowin, Melanie L. Schwandt, Nancy Diazgranados, Vijay A. Ramchandani
-
- Journal:
- Journal of Clinical and Translational Science / Volume 3 / Issue s1 / March 2019
- Published online by Cambridge University Press:
- 26 March 2019, pp. 154-155
-
- Article
-
- You have access Access
- Open access
- Export citation
-
OBJECTIVES/SPECIFIC AIMS: This study attempts to evaluate the drinking patterns and traits of individuals who partake in high intensity drinking, defined as binge drinking at 2 or more times the minimum binge count (4 drinks for females, 5 drinks for males). METHODS/STUDY POPULATION: We analyzed data from non-treatment seeking volunteers enrolled in NIAAA screening protocols. The sample included 706 males and 474 females ranging in age from 18 to 91. Subjects were assigned to one of four groups (Non-Binge, Level 1, Level 2, Level 3) based on the highest binge session reported in their Timeline Followback questionnaire. The criteria for each group were different for males and females based on the current NIAAA definitions of binge drinking. The cutoffs for females were 0-3 drinks for Non-Binge, 4-7 drinks for Level 1, 8-11 drinks for Level 2, and 12+ drinks for Level 3. The male drink cutoffs were 0-4, 5-9, 10-14, and 15+ respectively. We looked at various drinking measures (Timeline Followback, Self-Reported Effects of Alcohol (SRE), Alcohol Use Disorders Identification Test (AUDIT)) and trait measures (UPPS-P Impulsivity Scale, Barratt’s Impulsiveness Scale, Buss Perry Aggression Questionnaire) to identify mean differences between groups. RESULTS/ANTICIPATED RESULTS: There were significant differences in drinking patterns between the groups for both males and females. Number of drinking days, average drinks per drinking day, and number of heavy drinking days all increased as binge level increased. There were also significant differences between groups in males for trait measures. Level 2 and Level 3 bingers scored significantly higher on impulsivity and aggression than the Level 1 and Non-Binge groups. Ongoing analyses are examining differences among binge groups on other measures including SRE and AUDIT. Future analyses will explore potential mechanisms underlying the relationships between trait measures and binge drinking using structural equation modeling. DISCUSSION/SIGNIFICANCE OF IMPACT: This study found significant differences between high-intensity drinkers, or “super bingers”, and lighter binge and non-binge drinkers. Super bingers showed an overall heavier drinking pattern across measures. The elevated aggression, impulsivity, and overall heavy drinking patterns of super bingers suggest a behavioral profile that makes this group in particular at higher risk for developing alcohol use disorder and related problems. These traits and behaviors may also help identify targets for treatment interventions for alcohol use disorder.
3289 The Role of Suggestibility in Alcohol Use and Misuse
- Alexandra Cowand, Bethany L. Stangl, Melanie L. Schwandt, Alyssa Schneider, Jodi M. Gilman, Nancy Diazgranados, Vijay A. Ramchandani
-
- Journal:
- Journal of Clinical and Translational Science / Volume 3 / Issue s1 / March 2019
- Published online by Cambridge University Press:
- 26 March 2019, p. 156
-
- Article
-
- You have access Access
- Open access
- Export citation
-
OBJECTIVES/SPECIFIC AIMS: Suggestibility, defined as the inclination to accept and internalize messages, has not been assessed much in relation to alcohol use. Prior research has shown that suggestibility to social cues and peer influence may play a role in driving alcohol consumption. Our previous work has shown associations between suggestibility and alcohol consumption in social drinkers. This study aims to examine how suggestibility and social susceptibility are related to ideas alcohol consumption and consequences across the spectrum of alcohol use and misuse. We hypothesize that those with higher suggestibility and social susceptibility reports will also have higher alcohol consumption and consequences, and that the impact of susceptibility is lower in dependent compared to non-dependent drinkers. METHODS/STUDY POPULATION: Study participants enrolled in the NIAAA screening and assessment protocol (N=157) completed questionnaires on suggestibility and alcohol consumption, The Multidimensional Iowa Suggestibility Scale (MISS) is a 95-question self-report assessment of suggestibility which draws from subcategories of consumer suggestibility, perceivability, physiological suggestibility, physiological reactivity, and peer conformity. Alcohol measures included 90-day Timeline Followback interviews and the Alcohol Use Disorder Identification Test (AUDIT). Participants also underwent the Structured Clinical Interviews for DSM-IV or DSM-5 disorders, and were stratified into two groups: alcohol dependent (N = 86) and non-dependent (N=71). Median split by age was additionally used to explore age’s relationship with suggestibility and alcohol with the under 36 (N = 45) and over 36 (N = 26) non-dependent groups. RESULTS/ANTICIPATED RESULTS: Initial analyses showed marked differences between the dependent and non-dependent groups in the relationship between the MISS total score and AUDIT total score. The non-dependent group showed significant positive correlations between MISS and AUDIT scores (r = 0.460, p < 0.001), while the dependent group did not show any correlation between MISS and AUDIT scores. Further examination of these relationships in the nondependent group revealed that MISS scores were also significantly positively correlated with AUDIT subscores of consumption, harm, and dependence. Age was found to have a significant negative correlation with MISS score (r = −0.354, p < 0.01). To better understand the role of age, the sample was split based on the median age (36 yrs), and analyzed separately. Results indicated robust relationships between MISS score and AUDIT (r = 0.457, p < 0.01) in the younger age group. In addition, the younger age group also showed significant relationships between MISS score and 90-day TLFB measures of total drinks, days drinking, and heavy drinking days. DISCUSSION/SIGNIFICANCE OF IMPACT: In non-dependent individuals, there was a significant positive relationship between suggestibility and alcohol measures, and these effects were amplified in younger individuals. No relationship was found between suggestibility and alcohol measures in the alcohol dependent individuals. This may be related to a greater impact of social and external contextual cues in younger social drinkers compared to dependent drinkers where tolerance and craving may have greater impact on alcohol consumption. These findings have important implications for traits that may put individuals at risk for developing harmful patterns of alcohol use and misuse. Future analyses will aim to examine biobehavioral underpinnings of the relationship between suggestibility and alcohol consumption.
The serotonin transporter gene linked polymorphic region is associated with the behavioral response to repeated stress exposure in infant rhesus macaques
- Simona Spinelli, Melanie L. Schwandt, Stephen G. Lindell, Markus Heilig, Stephen J. Suomi, J. Dee Higley, David Goldman, Christina S. Barr
-
- Journal:
- Development and Psychopathology / Volume 24 / Issue 1 / February 2012
- Published online by Cambridge University Press:
- 31 January 2012, pp. 157-165
-
- Article
- Export citation
-
The short allele of the serotonin transporter linked polymorphic region (5-HTTLPR) moderates the effects of stress on vulnerability to mood and anxiety disorders. The mechanism by which this occurs may relate to differential sensitivity to stressful life events. Here we explored whether 5-HTTLPR and sex affected behavioral responses to repeated maternal separation in infant rhesus macaques. Behaviors were collected during the acute (Day 1) and the chronic (Days 2–4) phases of the separation, and the effects of duration of separation (acute vs. chronic), genotype (long/long vs. short allele), and sex (male vs. female) on behavioral responses were analyzed across four successive separations. Males increased their levels of locomotion with repeated maternal separation, whereas females exhibited an increase in frequency of self-directed behavior, a measure of “depression-like” behavior. The short-allele predicted increased environmental exploration, particularly during the chronic phase of social separation, indicative of higher arousal. In addition, the short-allele carriers were more likely to increase their levels of self-directed behavior during the chronic phase of separation, as a function of repeated exposures. These findings suggest that the short allele may increase reactivity to repeated, chronic stressors, leaving them more vulnerable to affective psychopathology, with females particularly vulnerable.
Association between the recombinant human serotonin transporter linked promoter region polymorphism and behavior in rhesus macaques during a separation paradigm
- Simona Spinelli, Melanie L. Schwandt, Stephen G. Lindell, Timothy K. Newman, Markus Heilig, Stephen J. Suomi, J. Dee Higley, David Goldman, Christina S. Barr
-
- Journal:
- Development and Psychopathology / Volume 19 / Issue 4 / Fall 2007
- Published online by Cambridge University Press:
- 11 October 2007, pp. 977-987
-
- Article
- Export citation
-
Human studies have suggested an association between a variable length polymorphism in the serotonin transporter gene promoter region and vulnerability to anxiety and depression. Relative to the long (l) allele, the short (s) allele increases the risk of developing depression in individuals exposed to stressful life events. An orthologue of the human variant is present in rhesus macaques and allows for studies in animals exposed to stress. Here, we used an established model of early life stress exposure, in which rhesus macaques are raised without adults in a group of peers (peer-only reared [PR]), or with their mothers. At 6 months of age, animals were subjected to 4-day long social separations for 4 consecutive weeks, with 3 days of reunion in between. Data were collected during both the acute (Day 1) and chronic phases (Days 2–4) of separation. Behavioral factors were separately extracted for each phase of separation. For acute separation, the behavioral factors generated were despair and behavioral pathology and, for the chronic phase despair, agitation, and behavioral pathology. During both phases of social separation, PR l/s animals were more likely to exhibit pathological behaviors, whereas PR l/l monkeys show higher levels of despair compared to the other three groups. These findings indicate that early stress affects the behavioral response to separation differently as a function of recombinant human serotonin transporter linked polymorphic repeat genotype and suggest that carriers of the s allele are not only more anxious but may also be more vulnerable to developing behavioral pathology in the face of chronic adversity.