Crym-positive striatal astrocytes gate perseverative behaviour.

Astrocytes are heterogeneous glial cells of the central nervous system1-3. However, the physiological relevance of astrocyte diversity for neural circuits and behaviour remains unclear. Here we show that a specific population of astrocytes in the central striatum expresses µ-crystallin (encoded by Crym in mice and CRYM in humans) that is associated with several human diseases, including neuropsychiatric disorders4-7. In adult mice, reducing the levels of µ-crystallin in striatal astrocytes through CRISPR-Cas9-mediated knockout of Crym resulted in perseverative behaviours, increased fast synaptic excitation in medium spiny neurons and dysfunctional excitatory-inhibitory synaptic balance. Increased perseveration stemmed from the loss of astrocyte-gated control of neurotransmitter release from presynaptic terminals of orbitofrontal cortex-striatum projections. We found that perseveration could be remedied using presynaptic inhibitory chemogenetics8, and that this treatment also corrected the synaptic deficits. Together, our findings reveal converging molecular, synaptic, circuit and behavioural mechanisms by which a molecularly defined and allocated population of striatal astrocytes gates perseveration phenotypes that accompany neuropsychiatric disorders9-12. Our data show that Crym-positive striatal astrocytes have key biological functions within the central nervous system, and uncover astrocyte-neuron interaction mechanisms that could be targeted in treatments for perseveration.

Is trait rumination associated with affective reactivity to the menstrual cycle? A prospective analysis.

BACKGROUND: A minority of naturally cycling individuals experience clinically significant affective changes across the menstrual cycle. However, few studies have examined cognitive and behavioral constructs that may maintain or worsen these changes. Several small studies link rumination with premenstrual negative affect, with authors concluding that a tendency to ruminate amplifies and perpetuates hormone-sensitive affective symptoms. Replication in larger samples is needed to confirm the validity of rumination as a treatment target. METHOD: 190 cycling individuals (M = 30.82 years; 61.1% Caucasian) were recruited for moderate perceived stress, a risk factor for cyclical symptoms. They completed the Rumination Response Scale at baseline, then reported daily affective and physical symptoms across 1-6 cycles. Multilevel growth models tested trait rumination as a predictor of baseline levels, luteal increases, and follicular decreases in symptoms. RESULTS: The degree of affective cyclicity was normally distributed across a substantial range, supporting feasibility of hypothesis tests and validating the concept of dimensional hormone sensitivity. Contrary to prediction, higher brooding did not predict levels or cyclical changes of any symptom. In a subsample selected for luteal increases in negative affect, brooding predicted higher baseline negative affect but still did not predict affective cyclicity. CONCLUSIONS: An individual's trait-like propensity to engage in rumination may not be a valid treatment target in premenstrual mood disorders. State-like changes in rumination should still be further explored, and well-powered prospective studies should explore other cognitive and behavioral factors to inform development of targeted psychological treatments for patients with cyclical affective symptoms.

Comparison of trait and state mind wandering among schizotypal, subclinically depressed, and control individuals.

BACKGROUND: Mind wandering is a common phenomenon in daily life. However, the manifestations and cognitive correlates of mind wandering in different subclinical populations remain unclear. In this study, these aspects were examined in individuals with schizotypal traits and individuals with depressive symptoms, i.e., subclinical populations of patients with schizophrenia and depression. METHODS: Forty-two individuals with schizotypal traits, 42 individuals with subclinical depression, and 42 controls were recruited to complete a mind wandering thought sampling task (state level) and a mind wandering questionnaire (trait level). Measures of rumination and cognitive functions (attention, inhibition, and working memory) were also completed by participants. RESULTS: Both subclinical groups exhibited more state and trait mind wandering than did the control group. Furthermore, individuals with schizotypal traits demonstrated more trait mind wandering than individuals with subclinical depression. Rumination, sustained attention, and working memory were associated with mind wandering. In addition, mind wandering in individuals with subclinical depression can be accounted for by rumination or attention, while mind wandering in individuals with high schizotypal traits cannot be accounted for by rumination, attention, or working memory. CONCLUSIONS: The results suggest that individuals with high schizotypal traits and subclinical depression have different patterns of mind wandering and mechanisms. These findings have implications for understanding the unique profile of mind wandering in subclinical individuals.

The link between anger and reactive aggression: Insights into anger rumination.

This study examined the mediating role of anger rumination in the relationship between anger and reactive aggression and the potential of adaptive anger rumination in reducing reactive aggression. Study 1, a two-wave longitudinal survey of 177 Chinese adolescents, showed that anger rumination mediated the relationship between anger and reactive aggression. Study 2, an experimental study with 160 university students, showed that the self-distanced group had lower aggression than the self-immersed group, and anger rumination mediated the impact of anger on reactive aggression in only the self-immersed group. These findings clarify the role of anger rumination concerning the relationship between anger and reactive-aggression and highlight the importance of self-distanced anger rumination in preventing reactive aggression among adolescents and young adults.

An integrative analysis of potential mechanisms of reduced positive affect in daily life in depression: an ESM study.

Decreased levels of positive affect (PA) are a hallmark of depression. Current models propose as potential main mechanisms a dysfunctional use of emotion regulation (ER) strategies (i.e. dampening, positive rumination), and a maladaptive activation of pro-hedonic goals. However, the role of these mechanisms in PA in daily life remains understudied. We used a 10-day ESM design to assess how these mechanisms influence each other and contribute to depressive symptomatology-related low momentary PA in 139 individuals. Higher depressive symptoms were associated with lower PA, pro-hedonic goals, more frequent use of positive rumination, and higher use of dampening. Further, experiencing higher levels of PA predicted lower following time point use of dampening in individuals with higher symptoms. Finally, using positive rumination was more beneficial (i.e. predicted higher PA increases one moment later) for individuals with higher symptomatology. Our findings suggest that moment-to-moment changes in PA daily life are affected by, and have an effect on, both pro-hedonic goals and the use of dampening and positive rumination, highlighting specific cognitive-affective mechanisms that should be considered when designing interventions aimed at improving low PA characterising depression symptomatology.

A latent profile analysis of moral emotions following moral transgressions.

OBJECTIVE: Moral transgressions (MTs), events that violate one's moral code, are associated with the moral emotions of guilt and shame. However, there may be different patterns by which people experience guilt and shame that affect distress following MTs. METHOD: Undergraduates (N = 1371) exposed to an MT completed self-report assessments. This study used latent profile analysis (LPA) to examine profiles based on guilt cognitions, internalized shame, and distress in relation to a reported MT. Cognitive flexibility, years since the MT, and deliberate and intrusive rumination were examined as variables to determine how these factors predicted profile membership. RESULTS: Results from the LPA revealed a three-profile solution: a low moral distress profile (n = 1002), a moderate moral distress profile (n = 262), and a shame prominent profile (n = 107). Results indicated that higher levels of deliberate and intrusive rumination and lower levels of cognitive flexibility significantly increased the likelihood of belonging to the moderate moral distress or shame prominent profiles compared to the low moral distress profile. Higher levels of intrusive rumination and lower levels of cognitive flexibility also significantly increased the likelihood of belonging to the shame prominent profile over the moderate distress profile. CONCLUSION: Three different profiles emerged, with the shame prominent profile being driven primarily by internalized shame. Results suggest that intrusive rumination and cognitive inflexibility are risk factors to experiencing adverse responses to MTs.

Rumination and threat-biased interpretation mediate posttraumatic stress and growth responses to military stressors.

We examined the role of rumination and threat-biased interpretation in stress and growth responses to military stressors. Two online surveys were completed by 183 (survey 1) and 393 (survey 2) currently serving or retired military personnel. The surveys measured exposure to potential military stressors (exposure to combat, witnessing the consequences of war, and perceived moral injury), posttraumatic stress symptomatology (PTSS), posttraumatic growth (PTG), and personal wellbeing, with survey 1 including measures of rumination, and survey 2 including a measure of threat-biased interpretation. Path analyses revealed that indirect paths from both witnessing the consequences of war and experiencing betrayal to PTSS were mediated by intrusive rumination and threat-biased interpretation, and that indirect paths from both betrayal and transgressions by others to PTG were mediated by deliberate rumination and threat-biased interpretation. The results reveal the idiosyncratic nature of military stressors, their differential involvement with cognitions that underpin rumination about past events and interpretation of current events, and their relevance to posttraumatic stress and growth in military personnel.

Hypostability in the default mode network and hyperstability in the frontoparietal control network of dynamic functional architecture during rumination.

The neural underpinnings of rumination can be characterized by its specific dynamic nature. Temporal stability is the stable and consistent representation of information by a distributed neural activity and connectivity pattern across brain regions. Although stability is a key feature of the brain's functional architecture, its profiles supporting rumination remain elusive. We characterized the stability of the whole-brain functional architecture during an induced, continuous rumination state and compared it with a well-constrained distraction state as the control condition in a group of healthy participants (N = 40). We further examined the relationship between stability in regions showing a significant effect on the rumination vs. distraction contrast and rumination traits. The variability of dynamic functional connectivities (FCs) among these regions was also explored to determine the potential coupling regions that drove the altered stability pattern during rumination. The results showed that rumination was characterized by a similar but altered stability profile compared with distraction and resting states. Comparison between rumination and distraction revealed that key regions of the default mode network (DMN), such as the medial prefrontal cortex (MPFC) and bilateral parahippocampal gyrus (PHG), which showed decreased stability while frontoparietal control network (FPCN) regions, including the inferior parietal lobule (IPL) and dorsal lateral prefrontal cortex (DLPFC), showed significantly enhanced stability in rumination compared with distraction. Additionally, stability in the MPFC and IPL was related to individual differences in rumination traits. Exploratory analysis of the variation in dynamic FCs suggested that higher stability in the IPL may be related to its less variable FCs with the PHG. Together, these findings implicated that rumination may be supported by the dissociated dynamic nature of hypostability in the DMN and hyperstability in the FPCN.

Prevent breaking bad: A proof of concept study of rebalancing the brain's rumination circuit with real-time fMRI functional connectivity neurofeedback.

Rumination, repetitively thinking about the causes, consequences, and one's negative affect, has been considered as an important factor of depression. The intrusion of ruminative thoughts is not easily controlled, and it may be useful to visualize one's neural activity related to rumination and to use that information to facilitate one's self-control. Real-time fMRI neurofeedback (rtfMRI-nf) enables one to see and regulate the fMRI signal from their own brain. This proof-of concept study utilized connectivity-based rtfMRI-nf (cnf) to normalize brain functional connectivity (FC) associated with rumination. Healthy participants were instructed to brake or decrease FC between the precuneus and the right temporoparietal junction (rTPJ), associated with high levels of rumination, while engaging in a self-referential task. The cnf group (n = 14) showed a linear decrease in the precuneus-rTPJ FC across neurofeedback training (trend [112] = -0.180, 95% confidence interval [CI] -0.330 to -0.031, while the sham group (n = 14) showed a linear increase in the target FC (trend [112] = 0.151, 95% CI 0.017 to 0.299). Although the cnf group showed a greater reduction in state-rumination compared to the sham group after neurofeedback training (p < .05), decoupled precuneus-rTPJ FC did not predict attenuated state-rumination. We did not find any significant aversive effects of rtfMRI-nf in all study participants. These results suggest that cnf has the capacity to influence FC among precuneus and rTPJ of a ruminative brain circuit. This approach can be applied to mood and anxiety patients to determine the clinical benefits of reduction in maladaptive rumination.

Semantic and prosodic threat processing in trait anxiety: is repetitive thinking influencing responses?

The present study attempts to identify how trait anxiety, measured as worry-level, affects the processing of threatening speech. Two experiments using dichotic listening tasks were implemented; where participants had to identify sentences that convey threat through three different information channels: prosody-only, semantic-only and both semantic and prosody (congruent threat). We expected different ear advantages (left or right) depending on task demands, information type, and worry level. We used a full Bayesian approach for statistical modelling and analysis. Main results indicate that as worry-level increases, participants' reaction times increase. We explain this effect by proposing a fourth stage, associated with goal-oriented deliberation, for a three-phasic multistep model of emotional language processing. Higher levels of trait anxiety could induce verbal repetitive thinking (i.e. worry and/or rumination), which might prolong the mentioned deliberation stages, thus slowing down responses.

Rumination, Catastrophizing, and Other-Blame: The Cognitive-Emotional Regulation Strategies Involved in Anxiety-Related Life Interference in Anxious Children.

Childhood anxiety problems have a great impact on the daily functioning of children and their families. The first objective of this study was to compare whether the use of cognitive-emotional regulation strategies differs in children with and without anxious symptomatology. A second objective was to analyze the possible mediating role of regulation strategies in the relationship between the presence of anxious symptomatology and its subsequent interference in children's lives. In total, 315 children (53.7% boys) between 8 and 12 years old participated. Mann-Whitney-Wilcoxon U-test was used to analyze differences in the use of cognitive-emotional regulation strategies between children with and without anxious symptomatology. In order to identify the cognitive-emotional regulation strategies which mediate the relation between anxiety and the consequent interference in children's lives, mediation analyses were carried out. As expected, children with anxious symptomatology used more maladaptive regulatory strategies than those without such symptomatology. Multiple mediation models in parallel showed that catastrophizing, rumination, and other-blame mediated the relationship between anxiety problems and their consequent interference. The identification of functional or dysfunctional patterns of cognitive-emotion regulation may favor the inclusion of new components in the evidence-based interventions currently available, in an attempt to increase rates of remission of anxiety.

Rumination and the default mode network: Meta-analysis of brain imaging studies and implications for depression.

Rumination is strongly and consistently correlated with depression. Although multiple studies have explored the neural correlates of rumination, findings have been inconsistent and the mechanisms underlying rumination remain elusive. Functional brain imaging studies have identified areas in the default mode network (DMN) that appear to be critically involved in ruminative processes. However, a meta-analysis to synthesize the findings of brain regions underlying rumination is currently lacking. Here, we conducted a meta-analysis consisting of experimental tasks that investigate rumination by using Signed Differential Mapping of 14 fMRI studies comprising 286 healthy participants. Furthermore, rather than treat the DMN as a unitary network, we examined the contribution of three DMN subsystems to rumination. Results confirm the suspected association between rumination and DMN activation, specifically implicating the DMN core regions and the dorsal medial prefrontal cortex subsystem. Based on these findings, we suggest a hypothesis of how DMN regions support rumination and present the implications of this model for treating major depressive disorder characterized by rumination.

The subsystem mechanism of default mode network underlying rumination: A reproducible neuroimaging study.

Rumination is a repetitive self-referential thinking style that is often interpreted as an expression of abnormalities of the default mode network (DMN) observed during "resting-state" in major depressive disorder (MDD). Recent evidence has demonstrated that the DMN is not unitary but can be further divided into 3 functionally heterogenous subsystems, although the subsystem mechanistically underlying rumination remains unclear. Due to the unconstrained and indirect correlational nature of previous resting-state fMRI studies on rumination's network underpinnings, a paradigm allowing direct investigation of network interactions during active rumination is needed. Here, with a modified continuous state-like paradigm, we induced healthy participants to ruminate or imagine objective scenarios (distraction, as a control condition) on 3 different MRI scanners. We compared functional connectivities (FC) of the DMN and its 3 subsystems between rumination and distraction states. Results yielded a highly reproducible and dissociated pattern. During rumination, within-DMN FC was generally decreased as compared to the distraction state. At the subsystem level, we found increased FC between the core and medial temporal lobe (MTL) subsystem as well as decreased FC between the core and dorsal medial prefrontal cortex (DMPFC) subsystem and within the MTL subsystem. Finally, subjects' behavioral measures of rumination and brooding were negatively correlated with FC between the core and DMPFC subsystems. These results suggest active rumination involves enhanced constraint by the core subsystem on the MTL subsystem and decreased coupling between the core and DMPFC subsystem, allowing for more information exchange among those involved DMN components. Furthermore, the reproducibility of our findings provides a rigorous evaluation of their validity and significance.

Tendency to ruminate and anxiety are associated with altered alpha and beta oscillatory power dynamics during memory for contextual details.

Rumination occurs when an individual becomes mentally stuck and cannot redirect attention away from an unwanted thought demonstrating cognitive inflexibility. Cognitive flexibility is important for various cognitive functions, including episodic memory. Trait rumination is a partial mediator in the relationship between depression and overgeneral episodic memory, suggesting that rumination may negatively influence memory for contextual details. Oscillations in the alpha (8-12 Hz) and beta (13-30 Hz) frequency bands are crucial for various cognitive functions (e.g., attention control and episodic memory) and may help to explain the relationship between trait rumination and memory for contextual details. Our study uses EEG recorded during a source memory task to assess how alpha and beta oscillations during memory for contextual details may change as a function of trait rumination, anxiety, and depression level (n = 43). The source memory task instructs participants to remember objects and their associated contextual details. Memory for contextual details is lessened for participants higher in trait rumination paired with higher trait anxiety. Oscillations were analyzed in posterior parietal/occipital regions. During encoding, an interaction of nonclinical depression level and rumination predicts higher alpha power for items that were later not successfully remembered. During test, depression and rumination interact and predict higher alpha power for both successful and unsuccessful memory. These results suggest that trait anxiety, depression, and rumination impact accuracy and alpha oscillatory dynamics during contextual memory via changes in attention control.

Personality characteristics and cognitive appraisals associated with self-discrepancy after severe traumatic brain injury.

Although changes to self-identity or self-discrepancy are common after severe traumatic brain injury (TBI), the mechanisms underlying these changes are poorly understood. This study aimed to examine the influence of personality characteristics and cognitive appraisals on self-discrepancy. Participants were 51 adults (74% male) with severe TBI (M age = 36.22 years; SD = 12.65) who were on average 34 months (SD = 40.29) post-injury. They completed self-report measures of personality style (optimism and defensiveness), cognitive appraisals (threat appraisals, rumination and reflection and perceived coping resources), and self-discrepancy (Head Injury Semantic Differential Scale - III). Correlation analyses identified that higher levels of optimism, defensiveness and perceived coping resources were significantly associated with more positive self-discrepancy (r = .29-.47, p < .05), whereas higher threat appraisals and rumination were significantly related to more negative self- discrepancy (r = -.50-.57, p < .001). After controlling for personality characteristics, cognitive appraisals significantly accounted for self-discrepancy (R2 change = .15). Moreover, rumination significantly mediated the relationship between optimism and self-discrepancy. In summary, cognitive appraisals were found to be related to self-discrepancy, independent of personality characteristics. Rumination in particular may be an important target of psychological intervention for individuals experiencing negative self-discrepancy.

Relationship between resilience and insomnia among the middle-aged and elderly: mediating role of maladaptive emotion regulation strategies.

This study aimed to investigate the relationships between cognitive emotion regulation (CER) strategies, resilience, and insomnia and the underlying mechanism that explains the relationships. Six hundred and fifty-three middle-aged and old people recruited from community service centers in Henan province completed questionnaires related to CER strategies, resilience, and insomnia. Results showed refocus on planning and positive reappraisal negatively predicted insomnia, and catastrophising, rumination and self-blame positively predicted insomnia. Moreover, maladaptive emotion regulation strategies (especially catastrophising) mediated the relationship between resilience and insomnia. The findings suggest the middle-aged and elderly with insomnia tended to employ maladaptive emotion regulation strategies and had lower resilience. Maladaptive emotion regulation strategies buffered the positive effect of resilience on sleep.

A multimethod assessment to study the relationship between rumination and gender differences.

Rumination is described as the propensity of responding to distress by repetitively and passively focusing on one's negative emotions, and failures, and their consequences (Nolen-Hoeksema, 1991, 1998). Therefore, given that rumination is characterized especially by difficulties in managing and controlling negative emotional states, it is considered as the most common (impaired) emotional regulation strategy, and can be defined as an emotional process related to a repetitive, undesired, and past-oriented negatively inclined thought (Compare, Zarbo, Shonin, Van Gordon, & Marconi, 2014; Smith & Alloy, 2009). Recent evidence suggested that because of problems related to monitoring of negative states, rumination may be associated with exaggerated physiological reactivity relative to demands from the environment, and to some difficulties in attentional control abilities. The current study aimed at deepening our understanding of the role that a maladaptive emotional regulation strategy - such as rumination - might play in physiological response changes and in engaging dysfunctional attentional strategies. We used a multimethod assessment including self-reports (i.e., Rumination and Reflection Questionnaire, and Difficulties in Emotion Regulation Scale), physiological measures, (i.e., Heart Rate Variability recording), and attention tasks (i.e., Stroop Task) in order to examine the multiple aspects of rumination across genders. Sixty-eight individuals (30 males and 38 females) were administered DERS -16, RRQ and, soon after them, the Stroop task. Immediately after completing the Stroop task (T1), participants were exposed to a three-phase, baseline-stress-recovery experimental paradigm while their heart rate variability (HRV) was recorded. After completing the experimental paradigm, Stroop stimuli were presented for the second time (T2), in order to examine possible intra-individual differences between the two performances in the Stroop task. Our findings showed that rumination was higher in females than in males, but in men it appeared to be strongly associated with an overall impaired emotional regulation. However, no gender differences in rumination and emotion dysregulation were found when inspecting physiological data. The current study aims to contribute towards a better understanding which emotion regulation strategies and which physiological mechanisms are associated with rumination.

Duration of Perseverative Thinking as Related to Perceived Stress and Blood Pressure: An Ambulatory Monitoring Study.

OBJECTIVE: Psychological distress may be intensified and prolonged by perseverative thinking (e.g., rumination, worry). The tendency to engage frequently in perseverative thinking has been linked to increased blood pressure (BP). Research is needed to investigate the physiological consequences of time spent perseverating by testing the momentary association between the duration of perseverative thinking and BP. The present study examines the extent to which the duration of perseverative thinking is associated with momentary perceived stress and ambulatory BP elevations during daily life. METHODS: Participants (N = 373) drawn from a larger project on BP and cardiovascular health completed 24-hour ambulatory BP monitoring accompanied by ecological momentary assessments of their perseverative thoughts and feelings. Multilevel models tested associations among perseveration duration, momentary perceived stress, and systolic and diastolic BP, adjusting for person-level and momentary covariates. RESULTS: Higher within-subject perseveration duration was associated with higher stress (B = 0.29; 95% confidence interval [CI] = 0.24-0.33; p < .001). Although higher perseveration duration was not associated with substantially higher systolic (B = 0.16 mm Hg; 95% CI = 0.00-0.33 mm Hg; p = .056) or diastolic (B = 0.07 mm Hg; 95% CI = -0.05 to 0.19 mm Hg; p = .25) BP, the associations between higher perseveration duration and higher systolic (p = .032) and diastolic (p = .036) BP were significantly mediated by a higher intensity of momentary perceived stress. CONCLUSIONS: Findings support the clinically important notion that physiological consequences of perceived stress can be maintained and even heightened by maladaptively prolonged mental activity.

Effects of 5-HTTLPR genotype and cognitive rumination on long-term cortisol reactivity measured in human hair.

Ample experimental and associative studies have shown that carrying two short (S) alleles of the serotonin transporter gene (5-HTTLPR) contributes to an increased vulnerability for stress and related affective disorders. Recent findings indicate that this relationship might become even more profound when also possessing a negative ruminative (stress-related) thinking style. However, previous studies on the relationship among 5-HTTLPR, stress, and stress-responsiveness almost exclusively measured salivary cortisol concentrations during exposure to a single acute (laboratory) stressor. Measuring cortisol concentrations over longer periods of time might better reflect (chronic) Gene by biological (HPA) stress responsiveness associations. In recent years, the strategy to assess hair cortisol concentration (HCC) has been established as a more reliable marker for chronic HPA activations. The current study explored associations between 3-months accumulated HCC and the tendency to ruminate about negative events in 27 S/S and 27 L/L 5-HTTLPR-carriers (screened from a large n = 827 DNA database). Hierarchical regression (including moderation) analyses revealed clear significant interactions between Genotype and Rumination (p < 0.01, f2=0.26); indicating greatest accumulation of HCC in high ruminating S/S-allele carriers. These findings implicate that the combined possession of a genetic (S-allele 5-HTTLPR) and cognitive (Rumination) stress-vulnerability might meaningfully increases long-term stress responsiveness; most likely due to increased daily (chronic) stress experiences. Lay summary The current study investigated whether the combined possession of a biological (genetic) and cognitive (negative thinking pattern) stress vulnerability may lead to a greater vulnerability to experience daily stress. This hypothesis was confirmed as a higher accumulation of the cortisol stress hormone was found over the past 3 months in scalp hair of participants that carried both vulnerability factors in combination.

Serotonin system genes and obsessive-compulsive trait dimensions in a population-based, pediatric sample: a genetic association study.

BACKGROUND: Serotonin system genes are commonly studied in obsessive-compulsive disorder (OCD), but genetic studies to date have produced inconsistent results, possibly because phenotypic heterogeneity has not been adequately accounted for. In this paper, we studied candidate serotonergic genes and homogenous phenotypic subgroups as presented through obsessive-compulsive (OC) trait dimensions in a general population of children and adolescents. We hypothesized that different serotonergic gene variants are associated with different OC trait dimensions and, furthermore, that they vary by sex. METHODS: Obsessive-compulsive trait dimensions (Cleaning/Contamination, Counting/Checking, Symmetry/Ordering, Superstition, Rumination, and Hoarding) were examined in a total of 5,213 pediatric participants in the community using the Toronto Obsessive-Compulsive Scale (TOCS). We genotyped candidate serotonin genes (directly genotyping the 5-HTTLPR polymorphism in SLC6A4 for 2018 individuals and using single nucleotide polymorphism (SNP) array data for genes SLC6A4, HTR2A, and HTR1B for 4711 individuals). We assessed the association between variants across these genes and each of the OC trait dimensions, within males and females separately. We analyzed OC traits as both (a) dichotomized based on a threshold value and (b) quantitative scores. RESULTS: The [LG + S] variant in 5-HTTLPR was significantly associated with hoarding in males (p-value of 0.003 and 0.004 for categorical and continuous analyses, respectively). There were no significant findings for 5-HTTLPR in females. Using SNP array data, there were significant findings for rumination in males for HTR2A SNPs (p-value of 1.04e-6 to 5.20e-6). CONCLUSIONS: This represents the first genetic association study of OC trait dimensions in a community-based pediatric sample. Our strongest results indicate that hoarding and rumination may be distinct in their association with serotonin gene variants and that serotonin gene variation may be specific to sex. Future genetic association studies in OCD should properly account for heterogeneity, using homogenous subgroups stratified by symptom dimension, sex, and age group.