Elevated interleukin-6 in women with binge-eating spectrum disorders.

OBJECTIVE: Binge-eating spectrum disorders (BESD) involve large eating episodes accompanied by a sense of loss of control that occur in individuals with body weights spanning the full body mass index (BMI) spectrum. While research links BESD with peripheral inflammation, this literature is limited by underpowered studies and a failure to control for confounding variables that could promote inflammation independent of dysregulated eating, specifically elevated body adiposity and depression. Our study examined plasma interleukin-6 (IL-6), a marker of peripheral inflammation, in a sample of women with BESD and non-eating disorder controls, controlling for BMI, body adiposity, and depression. METHOD: Participants (N = 94) included women with BESD (n = 73) or no eating disorder (n = 21) who completed structured clinical interviews in a larger study, selected to represent BMI categories ranging from underweight to obese in both groups. Fasting blood samples were processed for plasma IL-6 concentration via enzyme-linked immunosorbent assays. In addition to assessing group differences in plasma IL-6, exploratory analyses examined associations between IL-6 and biological and clinical markers of BESD. RESULTS: Significantly elevated plasma IL-6 was found in women with BESD, relative to controls, that was not accounted for by BMI, adiposity, or depression. Plasma IL-6 was positively correlated with plasma leptin concentration, clinical assessments of eating disorder severity, and participants' largest self-reported eating episode. DISCUSSION: Peripheral inflammation is specifically linked to presence of dysregulated eating independently from weight, adiposity, and depression in BESD. Future research should probe the potential role of neuroinflammation in altered eating behavior. PUBLIC SIGNIFICANCE: This study provides the first demonstration that inflammation, characterized by elevated plasma IL-6 concentration, is uniquely associated with dysregulated eating in a transdiagnostic group of individuals with BESD. A better understanding of whether immune factors contribute to dysregulated eating could help identify novel biological targets for intervention.

Disentangling the links between gastric emptying and binge eating v. purging in eating disorders using a case-control design.

BACKGROUND: Prior work supports delayed gastric emptying in anorexia nervosa and bulimia nervosa (BN) but not binge-eating disorder, suggesting that neither low body weight nor binge eating fully accounts for slowed gastric motility. Specifying a link between delayed gastric emptying and self-induced vomiting could offer new insights into the pathophysiology of purging disorder (PD). METHODS: Women (N = 95) recruited from the community meeting criteria for DSM-5 BN who purged (n = 26), BN with nonpurging compensatory behaviors (n = 18), PD (n = 25), or healthy control women (n = 26) completed assessments of gastric emptying, gut peptides, and subjective responses over the course of a standardized test meal under two conditions administered in a double-blind, crossover sequence: placebo and 10 mg of metoclopramide. RESULTS: Delayed gastric emptying was associated with purging with no main or moderating effects of binge eating in the placebo condition. Medication eliminated group differences in gastric emptying but did not alter group differences in reported gastrointestinal distress. Exploratory analyses revealed that medication caused increased postprandial PYY release, which predicted elevated gastrointestinal distress. CONCLUSIONS: Delayed gastric emptying demonstrates a specific association with purging behaviors. However, correcting disruptions in gastric emptying may exacerbate disruptions in gut peptide responses specifically linked to the presence of purging after normal amounts of food.

The Pattern of Fos-Like Immunoreactivity Expressed Within the Nucleus of the Solitary Tract Is Associated With Individual Variation in the Taste Quality of a Stimulus.

Outbred rats differ in their preference for the artificial sweetener sucralose. Psychophysical assessments have shown that the taste of sucralose is differentially generalized to either sucrose or a sucrose-quinine (QHCl) mixture in sucralose preferers (SP) and sucralose avoiders (SA), respectively. It remains to be determined if these differences in the psychophysical assessment of the taste of sucralose are due to an insensitivity to any bitter-like taste component of sucralose in SP or reduced sensitivity to a sweet-like component in SA that may mask any putative aversive side-taste in SP. Here, we exploited the proposed chemotopic organization of the rostral nucleus of the solitary tract (rNTS) to further parse out the root differences in the perception of the salient taste qualities of sucralose using Fos-like immunoreactivity (FLI) to approximate neural activation following intraoral delivery of sucrose, QHCl, and sucralose solutions in previously categorized SA and SP. First, we confirmed previous reports that the medial third of the NTS is primarily responsive to intraoral infusions of the bitter taste stimulus QHCl while sucrose produces a more diffuse pattern of FLI. Upon comparing the FLI generated by intraoral sucralose, we found that the pattern in SA was indistinguishable from that of QHCl while SP displayed a pattern of FLI more representative of a sucrose-QHCl mixture. We conclude that SA, relative to SP, may be less sensitive to the sucrose-like properties of sucralose and that an enhanced sensitivity to these sucrose-like qualities may mask a QHCl-like quality in SP.

Testosterone and cortisol do not predict rejecting harm or maximizing outcomes in sacrificial moral dilemmas: A preregistered analysis.

Contemporary moral psychology explores the biological underpinnings of morality, including how neuromodulators influence moral judgment and decision making. Some studies suggest that higher circulating testosterone is associated with increased acceptance of sacrificial harm, such as killing one person to save five lives, consistent with utilitarian ethics and inconsistent with deontological ethics. However, most studies employ conventional analytic techniques that conflate concern about outcomes with reduced concern about sacrificial harm, many are statistically underpowered, and none examine potential regulating effects of cortisol. Therefore, we examined whether salivary concentrations of testosterone and cortisol jointly predict sacrificial dilemma judgments among a large sample of undergraduates (n = 199). We utilized an advanced cognitive modeling technique (process dissociation) to independently assess sensitivity to causing harm and maximizing outcomes, preregistering the prediction that higher testosterone would predict reduced harm-rejection rather than increased concern for outcomes, especially among people low in cortisol. However, neither testosterone, nor cortisol, nor their interaction predicted sacrificial dilemma response tendencies. Such findings raise questions about the robustness of past evidence suggesting links between testosterone and sacrificial dilemma judgments.

Estradiol treatment attenuates high fat diet-induced microgliosis in ovariectomized rats.

Consumption of a high fat diet (HFD) increases circulating free fatty acids, which can enter the brain and promote a state of microgliosis, as defined by a change in microglia number and/or morphology. Most studies investigating diet-induced microgliosis have been conducted in male rodents despite well-documented sex differences in the neural control of food intake and neuroimmune signaling. This highlights the need to investigate how sex hormones may modulate the behavioral and cellular response to HFD consumption. Estradiol is of particular interest since it exerts a potent anorexigenic effect and has both anti-inflammatory and neuroprotective effects in the brain. As such, the aim of the current study was to investigate whether estradiol attenuates the development of HFD-induced microgliosis in female rats. Estradiol- and vehicle-treated ovariectomized rats were fed either a low-fat chow diet or a 60% HFD for 4 days, after which they were perfused and brain sections were processed via immunohistochemistry for microglia-specific Iba1 protein. Four days of HFD consumption promoted microgliosis, as measured via an increase in the number of microglia in the arcuate nucleus (ARC) of the hypothalamus and nucleus of the solitary tract (NTS), and a decrease in microglial branching in the ARC, NTS, lateral hypothalamus (LH), and ventromedial hypothalamus. Estradiol replacement attenuated the HFD-induced changes in microglia accumulation and morphology in the ARC, LH, and NTS. We conclude that estradiol has protective effects against HFD-induced microgliosis in a region-specific manner in hypothalamic and hindbrain areas implicated in the neural control of food intake.

Selective activation of estrogen receptors, ERα and GPER-1, rapidly decreases food intake in female rats.

Many of estradiol's behavioral effects are mediated, at least partially, via extra-nuclear estradiol signaling. Here, we investigated whether two estrogen receptor (ER) agonists, targeting ERα and G protein-coupled ER-1 (GPER-1), can promote rapid anorexigenic effects. Food intake was measured in ovariectomized (OVX) rats at 1, 2, 4, and 22 h following subcutaneous (s.c.) injection of an ERα agonist (PPT; 0-200 µg/kg), a GPER-1 agonist (G-1; 0-1600 µg/kg), and a GPER-1 antagonist (G-36; 0-80 µg/kg). To investigate possible cross-talk between ERα and GPER-1, we examined whether GPER-1 blockade affects the anorexigenic effect of PPT. Feeding was monitored in OVX rats that received s.c. injections of vehicle or 40 µg/kg G-36 followed 30 min later by s.c. injections of vehicle or 200 µg/kg PPT. Selective activation of ERα and GPER-1 alone decreased food intake within 1 h of drug treatment, and feeding remained suppressed for 22 h following PPT treatment and 4 h following G-1 treatment. Acute administration of G-36 alone did not suppress feeding at any time point. Blockade of GPER-1 attenuated PPT's rapid (within 1 h) anorexigenic effect, but did not modulate PPT's ability to suppress food intake at 2, 4 and 22 h. These findings demonstrate that selective activation of ERα produces a rapid (within 1 h) decrease in food intake that is best explained by a non-genomic signaling pathway and thus implicates the involvement of extra-nuclear ERα. Our findings also provide evidence that activation of GPER-1 is both sufficient to suppress feeding and necessary for PPT's rapid anorexigenic effect.

Sex differences in testosterone reactivity during marital conflict.

When attempting to resolve relationship problems, individuals in close relationships sometimes challenge their partners with statements that oppose their partners' point of view. Such oppositional behaviors may undermine those partners' relational value and threaten their status within the relationship. We examined whether perceptions of opposition from a partner during a series of problem-solving interactions were associated with reactivity in testosterone levels and whether those associations were different for men and women. Fifty newlywed couples discussed four marital problems. Each member of the couple reported how much oppositional behavior they perceived from their partner during the discussions. Pre- and post-discussion saliva samples were assayed for testosterone. For men, but not for women, perceptions of oppositional behavior were associated with heightened testosterone reactivity, and this result replicated across three different measures of testosterone reactivity. Findings were specific to men's perceptions of oppositional behavior, and held controlling for objective measures of oppositional behavior coded from videos of the conversations. Results highlight the benefits of considering pair-bonded relationships as a novel context for investigating associations involving hormones and behavior. Findings also raise the possibility that sex differentiated hormonal reactions to opposition partly explain why conflict among heterosexual partners can be so divisive.

Progesterone and women's anxiety across the menstrual cycle.

Animal models and a few human investigations suggest progesterone may be associated with anxiety. Progesterone naturally fluctuates across the menstrual cycle, offering an opportunity to understand how within-person increases in progesterone and average progesterone levels across the cycle correspond to women's anxiety. Across two longitudinal studies, we simultaneously modeled the between- and within-person associations between progesterone and anxiety using multilevel modeling. In Study 1, 100 Polish women provided saliva samples and reported their anxiety at three phases of the menstrual cycle: follicular, peri-ovulatory, and luteal. A significant between-person effect emerged, revealing that women with higher average progesterone levels across their cycles reported higher levels of anxiety than women with lower progesterone cycles. This effect held controlling for estradiol. In Study 2, 61 American women provided saliva samples and reported their attachment anxiety during laboratory sessions during the same three cycle phases. A significant between-person and within-person association emerged: women with higher average progesterone levels reported higher levels of attachment anxiety, and as women's progesterone levels increased across their cycles, so too did their attachment anxiety. These effects held controlling for cortisol. In sum, both studies provide support for a link between menstrual cycle progesterone levels and subjective anxiety.

Disturbance of gut satiety peptide in purging disorder.

OBJECTIVE: Little is known about biological factors that contribute to purging after normal amounts of food-the central feature of purging disorder (PD). This study comes from a series of nested studies examining ingestive behaviors in bulimic syndromes and specifically evaluated the satiety peptide YY (PYY) and the hunger peptide ghrelin in women with PD (n = 25), bulimia nervosa-purging (BNp) (n = 26), and controls (n = 26). Based on distinct subjective responses to a fixed meal in PD (Keel, Wolfe, Liddle, DeYoung, & Jimerson, ), we tested whether postprandial PYY response was significantly greater and ghrelin levels significantly lower in women with PD compared to controls and women with BNp. METHOD: Participants completed structured clinical interviews, self-report questionnaires, and laboratory assessments of gut peptide and subjective responses to a fixed meal. RESULTS: Women with PD demonstrated a significantly greater postprandial PYY response compared to women with BNp and controls, who did not differ significantly. PD women also endorsed significantly greater gastrointestinal distress, and PYY predicted gastrointestinal intestinal distress. Ghrelin levels were significantly greater in PD and BNp compared to controls, but did not differ significantly between eating disorders. Women with BNp endorsed significantly greater postprandial hunger, and ghrelin predicted hunger. DISCUSSION: PD is associated with a unique disturbance in PYY response. Findings contribute to growing evidence of physiological distinctions between PD and BNp. Future research should examine whether these distinctions account for differences in clinical presentation as this could inform the development of specific interventions for patients with PD.

Estradiol modulates the anorexic response to central glucagon-like peptide 1.

Estrogens suppress feeding in part by enhancing the response to satiation signals. Glucagon-like peptide 1 (GLP-1) acts on receptor populations both peripherally and centrally to affect food intake. We hypothesized that modulation of the central GLP-1 system is one of the mechanisms underlying the effects of estrogens on feeding. We assessed the anorexic effect of 0, 1, and 10µg doses of GLP-1 administered into the lateral ventricle of bilaterally ovariectomized (OVX) female rats on a cyclic regimen of either 2µg ß-estradiol-3-benzoate (EB) or oil vehicle 30min prior to dark onset on the day following hormone treatment. Central GLP-1 treatment significantly suppressed food intake in EB-treated rats at both doses compared to vehicle, whereas only the 10µg GLP-1 dose was effective in oil-treated rats. To follow up, we examined whether physiologic-dose cyclic estradiol treatment influences GLP-1-induced c-Fos in feeding-relevant brain areas of OVX females. GLP-1 significantly increased c-Fos expression in the area postrema (AP) and nucleus of the solitary tract (NTS), and the presence of estrogens may be required for this effect in the paraventricular nucleus of the hypothalamus (PVN). Together, these data suggest that modulation of the central GLP-1 system may be one of the mechanisms by which estrogens suppress food intake, and highlight the PVN as a region of interest for future investigation.

The association between affective psychopathic traits, time incarcerated, and cortisol response to psychosocial stress.

Previous research has demonstrated that psychopathic personality traits are significantly predictive of blunted cortisol reactivity to a performance-based stressor task (Trier Social Stress Test; TSST) in college students. However, the relationship between cortisol reactivity and psychopathy has not been explored in high risk samples such as incarcerated populations. Further, the role of imprisonment in relation to cortisol stress reactivity has not been previously explored, but could have practical and conceptual consequences in regard to rehabilitation and biological sensitivity to context, respectively. The current study tested the hypotheses that both psychopathic personality traits and amount of time incarcerated are related to cortisol blunting in response to stress among incarcerated young adults. A sample of 49 young adult male offenders was recruited to complete the TSST. Salivary hormone samples were taken just prior to and 20 min post-stressor, and participants were interviewed with the Psychopathy Checklist-Youth Version. Variables quantifying the amount of time at the present facility prior to the date of testing and number of commitments in juvenile facilities were also collected. Correlational analyses indicated that only number of incarcerations was related to blunted cortisol. Hierarchical Linear Modeling revealed that time incarcerated and number of commitments were related to a blunted cortisol response among responders and declining cortisol reactivity among nonresponders, respectively. Controlling for time incarcerated, psychopathic traits were significantly related to cortisol decline in response to the stressor among nonresponders, but were not related to blunted cortisol among responders. Results of this project highlight the potential biological effects of prolonged and repeated incarcerations, and extend our understanding about the relationship between psychopathic traits and cortisol reactivity in an incarcerated sample.

Preliminary examination of glucagon-like peptide-1 levels in women with purging disorder and bulimia nervosa.

OBJECTIVE: This study examined pre- and postprandial glucagon-like peptide 1 (GLP-1) levels in women with bulimia nervosa (BN), purging disorder (PD), and non-eating disorder control women to better understand whether alterations in satiation-related hormones in BN may be linked to binge-eating episodes or other altered ingestive behaviors. METHOD: Participants included women with BN (n = 19), PD (n = 14), or controls (n = 14). Participants provided subjective ratings for hunger and fullness and plasma samples before and after consumption of a standardized test meal. RESULTS: As expected, GLP-1 levels increased significantly following test meal consumption; however, participants with BN displayed significantly lower GLP-1 levels compared to PD and control participants both before and after consumption of the test meal. There were no significant differences between PD and control participants in GLP-1 levels, but individuals with PD displayed significantly higher levels of fullness throughout the test meal as compared to both control and BN participants. DISCUSSION: Our findings provide preliminary evidence that reduced GLP-1 levels in individuals with BN may be associated with binge-eating episodes. Additionally, increased fullness in individuals with PD does not appear to be accounted for by exaggerated postprandial GLP-1 release.

Determinants of taste preference and acceptability: quality versus hedonics.

Several methods exist for reliably determining the motivational valence of a taste stimulus in animals, but few to determine its perceptual quality independent of its apparent affective properties. Individual differences in taste preference and acceptability could result from variance in the perceptual qualities of the stimulus leading to different hedonic evaluations. Alternatively, taste perception might be identical across subjects, but the processing of the sensory signals in reward circuits could differ. Using an operant-based taste cue discrimination/generalization task involving a gustometer, we trained male Long-Evans rats to report the degree to which a test stimulus resembled the taste quality of either sucrose or quinine regardless of its intensity. The rats, grouped by a characteristic bimodal phenotypic difference in their preference for sucralose, treated this artificial sweetener as qualitatively different-compared to sucralose-avoiding rats, the sucralose-preferring rats found the stimulus much more perceptually similar to sucrose. Although the possibility that stimulus palatability may have served as a discriminative cue cannot entirely be ruled out, the profile of results suggests otherwise. Subsequent brief-access licking tests revealed that affective licking responses of the same sucralose-avoiding and -preferring rats differed across concentration in a manner approximately similar to that found in the stimulus generalization task. Thus, the perceived taste quality of sucralose alone may be sufficient to drive the observed behavioral avoidance of the compound. By virtue of its potential ability to dissociate the sensory and motivational consequences of a given experimental manipulation on taste-related behavior, this approach could be interpretively valuable.

Preference for sucralose predicts behavioral responses to sweet and bittersweet tastants.

Rats can be classified as either sucralose avoiders (SA) or sucralose preferrers (SP) based on their behavioral responses in 2-bottle preference, 1-bottle intake, and brief-access licking tests. The present study demonstrates that this robust phenotypic variation in the preference for sucralose predicts acceptance of saccharin, an artificial sweetener with a purported concentration-dependent "bitter" side taste and a 0.25 M sucrose solution adulterated with increasing concentrations of quinine hydrochloride (QHCl). Specifically, SA displayed decreased preference for and intakes of saccharin (≥41.5 mM) and sucrose-QHCl (>0.5 mM QHCl) solutions, relative to SP. In a second experiment involving brief-access (30-s) tests, SP and SA did not differ in their unconditioned licking responses across a range of sodium chloride or QHCl solutions (0.03-1 mM). However, the acceptability threshold for sucrose was lower in SA, relative to SP (0.06 and 0.13 M, respectively). Our findings suggest that phenotypic differences in sucralose preference are indicative of a more general difference in the hedonic processing of stimuli containing "bittersweet" or "sweet" taste qualities.

Systemic 5-bromo-2-deoxyuridine induces conditioned flavor aversion and c-Fos in the visceral neuraxis.

5-bromo-2-deoxyuridine (BrdU) is often used in studies of adult neurogenesis and olfactory learning, but it can also have toxic effects on highly proliferative tissue. We found that pairing Kool-Aid flavors with acute systemic injections of BrdU induced strong conditioned flavor aversions. Intermittent injections during Kool-Aid-glucose conditioning interfered with learning of a conditioned flavor-nutrient preference. Acute injection of BrdU also elevated plasma corticosterone levels and induced c-Fos in the visceral neuraxis. Thus, acute or intermittent systemic injections of BrdU (50-200 mg/kg) have aversive effects that may interfere with learning.

An empirical investigation of the roles of biological, relational, cognitive, and emotional factors in explaining sex differences in dyadic sexual desire.

One challenge many marital couples face is that they experience discrepant levels of sexual desire for one another. Such discrepancies are particularly likely to arise in mixed-sex relationships because, at least in long-term relationships, men tend to have higher levels of sexual desire for their partner than do women. But what underlies this sex difference? We used a dyadic study of 100 mixed-sex community-based newlywed spouses to investigate the role of biological, relational, cognitive, and emotional factors in explaining sex differences in dyadic sexual desire for a long-term partner. Consistent with predictions, wives on average reported lower daily sexual desire for their spouse than did husbands. Moreover, individual differences in men's and women's levels of circulating testosterone explained this sex difference whereas relational (marital satisfaction, commitment), cognitive (sex-role identification, stress, self-esteem), and emotional (mood, depressive symptoms) factors did not. These findings advance our knowledge of factors that influence dyadic sexual desire and may have practical implications for treating relationship distress in mixed-sex marriages.

Rats display a robust bimodal preference profile for sucralose.

Female Sprague-Dawley rats display considerable variability in their preference for the artificial sweetener sucralose over water. While some rats can be classified as sucralose preferrers (SP), as they prefer sucralose across a broad range of concentrations, others can be classified as sucralose avoiders (SA), as they avoid sucralose at concentrations above 0.1 g/L. Here, we expand on a previous report of this phenomenon by demonstrating, in a series of 2-bottle 24-h preference tests involving water and an ascending series of sucralose concentrations, that this variability in sucralose preference is robust across sex, stage of the estrous cycle, and 2 rat strains (Long-Evans and Sprague-Dawley). In a second experiment involving a large sample of rats (n = 50), we established that the ratio of SP to SA is approximately 35-65%. This bimodal behavioral response to sucralose appears to be driven by taste because rats display a similar bimodal licking response to a range of sucralose solutions presented during brief-access tests. Finally, we have shown that sucralose avoidance is extremely robust as 23-h water-deprived SA continue to avoid sucralose in 1-h single-bottle intake tests. Based on their reduced licking responses to sucralose during brief-access (taste driven) tests, and the fact that their distaste for sucralose cannot be overcome by the motivation to rehydrate, we conclude that SA detect a negative taste quality of sucralose that SP are relatively insensitive to.

Estradiol acts in the medial preoptic area, arcuate nucleus, and dorsal raphe nucleus to reduce food intake in ovariectomized rats.

Estradiol (E2) exerts an inhibitory effect on food intake in a variety of species. While compelling evidence indicates that central, rather than peripheral, estrogen receptors (ERs) mediate this effect, the exact brain regions involved have yet to be conclusively identified. In order to identify brain regions that are sufficient for E2's anorectic effect, food intake was monitored for 48 h following acute, unilateral, microinfusions of vehicle and two doses (0.25 and 2.5 µg) of a water-soluble form of E2 in multiple brain regions within the hypothalamus and midbrain of ovariectomized rats. Dose-related decreases in 24-h food intake were observed following E2 administration in the medial preoptic area (MPOA), arcuate nucleus (ARC), and dorsal raphe nucleus (DRN). Within the former two brain areas, the larger dose of E2 also decreased 4-h food intake. Food intake was not influenced, however, by similar E2 administration in the paraventricular nucleus, lateral hypothalamus, or ventromedial nucleus. These data suggest that E2-responsive neurons within the MPOA, ARC, and DRN participate in the estrogenic control of food intake and provide specific brain areas for future investigations of the cellular mechanism underlying estradiol's anorexigenic effect.

The Role of the Gut Microbiome, Immunity, and Neuroinflammation in the Pathophysiology of Eating Disorders.

There is a growing recognition that both the gut microbiome and the immune system are involved in a number of psychiatric illnesses, including eating disorders. This should come as no surprise, given the important roles of diet composition, eating patterns, and daily caloric intake in modulating both biological systems. Here, we review the evidence that alterations in the gut microbiome and immune system may serve not only to maintain and exacerbate dysregulated eating behavior, characterized by caloric restriction in anorexia nervosa and binge eating in bulimia nervosa and binge eating disorder, but may also serve as biomarkers of increased risk for developing an eating disorder. We focus on studies examining gut dysbiosis, peripheral inflammation, and neuroinflammation in each of these eating disorders, and explore the available data from preclinical rodent models of anorexia and binge-like eating that may be useful in providing a better understanding of the biological mechanisms underlying eating disorders. Such knowledge is critical to developing novel, highly effective treatments for these often intractable and unremitting eating disorders.

CD38 is associated with bonding-relevant cognitions and relationship satisfaction over the first 3 years of marriage.

Although there are numerous benefits to having a satisfying romantic relationship, maintaining high levels of relationship satisfaction is difficult. Many couples experience declines in relationship satisfaction in the early years of marriage, and such declines predict not only relationship dissolution but also poor mental and physical health. Several recent studies indicate that genetic variation on the CD38 gene (CD38), at the single nucleotide polymorphism (SNP) rs3796863, is associated with cognitions and behaviors related to pair bonding; we thus leveraged longitudinal data from a sample of newlywed couples (N = 139 genotyped individuals; 71 couples) to examine whether rs3796863 is associated with relationship maintenance processes and, in turn, relationship satisfaction in the early years of marriage. Replicating and extending prior research, we found that individuals with the CC genotype (vs. AC/AA) of rs3796863 reported higher levels of gratitude, trust, and forgiveness and that trust mediated the association between rs3796863 and marital satisfaction. Moreover, the benefits conferred to CC individuals lasted over the first 3 years of marriage. To our knowledge, this is the first study to examine the link between variation in CD38 rs3796863 and marital functioning over time.