"Pathways": A hope-enhancing intervention for patients undergoing treatment for advanced lung cancer.

OBJECTIVE: Observational data suggest hope is associated with the quality of life and survival of people with cancer. This trial examined the feasibility, acceptability, and preliminary outcomes of "Pathways," a hope intervention for people in treatment for advanced lung cancer. METHODS: Between 2020 and 2022, we conducted a single-arm trial of Pathways among participants who were 3-12 weeks into systemic treatment. Pathways consisted of two individual sessions delivered during infusions and three phone calls in which participants discussed their values, goals, and goal strategies with a nurse or occupational therapist. Participants completed standardized measures of hope and goal interference pre- and post-intervention. Feasibility was defined as ≥60% of eligible patients enrolling, ≥70% of participants completing three or more sessions, ≥70% of participants completing post-assessments, and mean acceptability ratings ≥7 out of 10 on intervention relevance, helpfulness, and convenience. Linear regression fixed effects models with covariates modeled pre-post changes in complete case analysis and multiple imputation models. RESULTS: Fifty two participants enrolled: female (59.6%), non-Hispanic White (84.6%), rural (75.0%), and with low educational attainment (51.9% high school degree or less). Except for enrollment (54%), feasibility and acceptability markers were surpassed (77% adherence, 77% retention, acceptability ratings ≥8/10). There was moderate improvement in hope and goal interference from pre-to post-intervention (d = 0.51, p < 0.05 for hope; d = -0.70, p < 0.005 for goal interference). CONCLUSIONS: Strong feasibility, acceptability, and patient-reported outcome data suggest Pathways is a promising intervention to increase hope and reduce cancer-related goal interference during advanced lung cancer treatment.

Real-World Evidence Comparing Vedolizumab and Ustekinumab in Antitumor Necrosis Factor-Experienced Patients With Crohn's Disease.

INTRODUCTION: Many patients with Crohn's disease (CD) lose response or become intolerant to antitumor necrosis factor (TNF) therapy and subsequently switch out of class. We compared the effectiveness and safety of ustekinumab to vedolizumab in a large, geographically diverse US population of TNF-experienced patients with CD. METHODS: We conducted a retrospective cohort study using longitudinal claims data from a large US insurer (Anthem, Inc.). We identified patients with CD initiating vedolizumab or ustekinumab with anti-TNF treatment in the prior 6 months. Our primary outcome was treatment persistence for >52 weeks. Secondary outcomes included (i) all-cause hospitalization, (ii) hospitalization for CD with surgery, (iii) hospitalization for CD without surgery, and (iv) hospitalization for infection. Propensity score fine stratification was used to control for demographic and baseline clinical characteristics and prior treatments. RESULTS: Among 885 new users of ustekinumab and 490 new users of vedolizumab, we observed no difference in treatment persistence (adjusted risk ratio 1.09 [95% confidence interval 0.95-1.25]). Ustekinumab was associated with a lower rate of all-cause hospitalization (adjusted hazard ratio 0.73 [0.59-0.91]), nonsurgical CD hospitalization (adjusted hazard ratio 0.58 [0.40-0.83]), and hospitalization for infection (adjusted hazard ratio 0.56 [0.34-0.92]). DISCUSSION: This real-world comparative effectiveness study of anti-TNF-experienced patients with CD initiating vedolizumab or ustekinumab showed similar treatment persistence rates beyond 52 weeks, although secondary outcomes such as all-cause hospitalizations, nonsurgical CD hospitalizations, and hospitalizations for infection favored ustekinumab initiation. We, therefore, advocate for individualized decision making in this medically refractory population, considering patient preference and other factors such as cost and route of administration.

The natural trajectory of smoking cessation among cancer patients who want to quit "on their own": A mixed-methods, longitudinal study.

INTRODUCTION: Many cancer patients who smoke cigarettes want to quit. Unfortunately, many of these cancer patients prefer to quit without the aid of pharmacotherapy or behavioral counseling. The teachable moment of cancer diagnosis might still position these cancer patients to make meaningful changes in their smoking behavior, but no study has documented the trajectory of smoking cessation outcomes among cancer patients who want to quit "on their own". This study aimed to fill this gap in the literature. METHODS: In this mixed-methods, longitudinal study, 35 cancer patients who declined tobacco treatment because of the desire to quit "on their own" provided data via three surveys and 1-2 semi-structured interviews. The observation period spanned 60 days. Participants were recently diagnosed at and recruited from outpatient cancer clinics. RESULTS: Participants were mostly female (68.57%), White, non-Hispanic (85.71%), unemployed due to disability (57.14%), and rural residents (54.29%). Across time, 43.76% of participants achieved 50% smoking reduction, 21.88% achieved 3-day floating abstinence, 18.75% achieved 7-day floating abstinence, and 12.50% achieved 30-day point prevalence abstinence. Key themes that emerged from the interviews centered on intention and confidence to quit and types of tobacco treatment used/received. CONCLUSIONS: This study with cancer patients who desired to quit smoking without assistance found some evidence of quit success, but success waned as criteria grew more stringent. Results showed participants' initial intention to quit unassisted was quite strong, as few reported tobacco treatment use. Interventions to increase uptake of evidence-based tobacco treatment among cancer patients is sorely needed. IMPLICATIONS: The preference to quit smoking without assistance is common among cancer patients, even given lack of evidence supporting its effectiveness. This study is the first to explore the trajectory of smoking cessation outcomes among cancer patients who desire to quit without assistance. These data can be used to develop interventions to increase uptake of tobacco treatment and increase quit success among cancer patients.

Variability in caregiver attention bias to threat: A Goldilocks effect in infant emotional development?

Attention biases to threat are considered part of the etiology of anxiety disorders. Attention bias variability (ABV) quantifies intraindividual fluctuations in attention biases and may better capture the relation between attention biases and psychopathology risk versus mean levels of attention bias. ABV to threat has been associated with attentional control and emotion regulation, which may impact how caregivers interact with their child. In a relatively diverse sample of infants (50% White, 50.7% female), we asked how caregiver ABV to threat related to trajectories of infant negative affect across the first 2 years of life. Families were part of a multi-site longitudinal study, and data were collected from 4 to 24 months of age. Multilevel modeling examined the effect of average caregiver attention biases on changes in negative affect. We found a significant interaction between infant age and caregiver ABV to threat. Probing this interaction revealed that infants of caregivers with high ABV showed decreases in negative affect over time, while infants of caregivers with low-to-average ABV showed potentiated increases in negative affect. We discuss how both high and extreme patterns of ABV may relate to deviations in developmental trajectories.

Proposing a Model of Proactive Outreach to Advance Clinical Research and Care Delivery for Patients Who Use Tobacco.

There are evidence-based treatments for tobacco dependence, but inequities exist in the access to and reach of these treatments. Traditional models of tobacco treatment delivery are "reactive" and typically provide treatment only to patients who are highly motivated to quit and seek out tobacco treatment. Newer models involve "proactive" outreach, with benefits that include increasing access to tobacco treatment, prompting quit attempts among patients with low motivation, addressing health disparities, and improving population-level quit rates. However, the definition of "proactive" is not clear, and adoption has been slow. This commentary introduces a comprehensive yet flexible model of proactive outreach and describes how proactive outreach can optimize clinical research and care delivery in these domains: (1) identifying the population, (2) offering treatment, and (3) delivering treatment. Dimensions relevant to each domain are the intensity of proactive outreach (low to high) and the extent to which proactive outreach activities rely on human interaction or are facilitated by information technology (IT). Adoption of the proposed proactive outreach model could improve the precision and rigor with which tobacco cessation research and tobacco treatment programs report data, which could have a positive effect on care delivery and patient outcomes.

The State of the Science on Cancer Diagnosis as a "Teachable Moment" for Smoking Cessation: A Scoping Review.

INTRODUCTION: Theoretically, a cancer diagnosis has the potential to spur health behavior changes in physical activity, diet, substance use, medication adherence, and the like. The Teachable Moment heuristic is a parsimonious, transtheoretical framework for understanding the conditions under which behavior change might occur, with constructs that include affective, cognitive, and social factors. Application of the Teachable Moment to smoking cessation after cancer diagnosis might aid selection of predictors in observational studies and inform how to optimally design interventions to promote quit attempts and sustain abstinence, as many smoking cessation interventions for cancer survivors do not yield positive outcomes. AIMS AND METHODS: This scoping review of 47 studies that span nearly 20 years of literature examines the measurement of the Teachable Moment constructs and what empirical support they have in explaining cancer survivors' smoking behavior. RESULTS: From this review, it appears the construct of affective response is more widely explored than risk perceptions, social role, and self-concept. Strong, negative affective responses (e.g., anxiety, general distress) may be a powerful contributor to continued smoking after a cancer diagnosis. Risk perceptions may also play a role in smoking behavior, such that never and former smokers espouse stronger perceptions of smoking-related risks than current smokers. Finally, due to a paucity of studies, the role of cancer survivors' self-concept (e.g., identity as a "cancer survivor") and changes in their social role (e.g., employee, athlete) are unclear contributors to their smoking behavior. In summary, the Teachable Moment holds promise in its application to smoking cessation after a cancer diagnosis, though more direct research is needed. CONCLUSIONS: This scoping review of the scientific literature is the first formal test of the extent to which cancer diagnosis has been explored as a "teachable moment" for smoking cessation, with results that provide insight into issues of measurement precision and breadth as well as empirical support of the "teachable moment" heuristic.

A Daily Assessment Study of Smoking Cessation After a Head and Neck Cancer Diagnosis.

INTRODUCTION: This intensive longitudinal study describes key events in the process of smoking cessation after a new head and neck cancer (HNC) diagnosis. Prior longitudinal studies show some cancer patients quit, while others continue to smoke, but details about the pattern in which these discrete outcomes arise are scarce. This study is meant to help rectify this gap in the literature. AIMS AND METHODS: Participants were 42 HNC patients who reported current smoking at enrollment. Participants were recruited from an outpatient oncology clinic and completed a baseline questionnaire prior to begin a 30-day daily assessment. RESULTS: Few participants (9.52%) achieved 30-day continuous abstinence from smoking. On average, participants reported 9.64 ± 11.93 total days of abstinence. Nearly, all (94.44%, n = 34) participants made at least one quit attempt, with an average of 16.94 ± 11.30 quit attempt days. Fewer participants were able to achieve a 24-hour quit attempt (52.78%, n = 19), with a corresponding average of 5.50 ± 8.69 24-hour days. The median time to first 24-hour quit attempt was 13 days after enrollment. Based on smoking behavioral patterns, participants were categorized into five groups, the most common being "persistent attempters," which involved unsuccessful quit attempts throughout the study. Only 45% of participants (n = 19) used evidence-based treatment, the most common being cessation medication. CONCLUSIONS: This intensive longitudinal study found that cancer diagnosis can spur a lot of efforts to quit smoking. Unfortunately, this study suggests that many quit attempts are short lived, possibly a result of an absence or insufficient use of evidence-based treatments. IMPLICATIONS: For adults who are current smokers at the time of cancer diagnosis, there is a high likelihood of persistent cigarette smoking and use of other tobacco products in the weeks and months after a cancer diagnosis. Furthermore, this study shows that while a lot of quit attempts may occur, few are successful, which may be partly attributable to the low use of evidence-based tobacco treatment. Future research with cancer patients should aim to identify predictors of quit attempts and abstinence as well as treatment utilization.

Developmental patterns of affective attention across the first 2 years of life.

This study examined patterns of attention toward affective stimuli in a longitudinal sample of typically developing infants (N = 357, 147 females, 50% White, 22% Latinx, 16% African American/Black, 3% Asian, 8% mixed race, 1% not reported) using two eye-tracking tasks that measure vigilance to (rapid detection), engagement with (total looking toward), and disengagement from (latency to looking away) emotional facial configurations. Infants completed each task at 4, 8, 12, 18, and 24 months of age from 2016 to 2020. Multilevel growth models demonstrate that, over the first 2 years of life, infants became faster at detecting and spent more time engaging with angry over neutral faces. These results have implications for our understanding of the development of affect-biased attention.

Moderating effects of environmental stressors on the development of attention to threat in infancy.

An attention bias to threat has been linked to psychosocial outcomes across development, including anxiety (Pérez-Edgar, K., Bar-Haim, Y., McDermott, J. M., Chronis-Tuscano, A., Pine, D. S., & Fox, N. A. (2010). Attention biases to threat and behavioral inhibition in early childhood shape adolescent social withdrawal. Emotion (Washington, D.C.), 10(3), 349). Although some attention biases to threat are normative, it remains unclear how these biases diverge into maladaptive patterns of emotion processing for some infants. Here, we examined the relation between household stress, maternal anxiety, and attention bias to threat in a longitudinal sample of infants tested at 4, 8, and 12 months. Infants were presented with a passive viewing eye-tracking task in which angry, happy, or neutral facial configurations appeared in one of the four corners of a screen. We measured infants' latency to fixate each target image and collected measures of parental anxiety and daily hassles at each timepoint. Intensity of daily parenting hassles moderated patterns of attention bias to threat in infants over time. Infants exposed to heightened levels of parental hassles became slower to detect angry (but not happy) facial configurations compared with neutral faces between 4 and 12 months of age, regardless of parental anxiety. Our findings highlight the potential impact of the environment on the development of infants' early threat processing and the need to further investigate how early environmental factors shape the development of infant emotion processing.

Personality Traits Predict Long-Term Physical Health via Affect Reactivity to Daily Stressors.

Researchers hypothesize that how people react to daily stressful events partly explains the relationship between personality and health, yet no study has examined longitudinal associations between these factors. The current study focused on the role of negative affect reactivity to daily stressful events as a mediating pathway between personality and physical health outcomes using three waves of data spanning 20 years from a nationwide probability sample of 1,176 adults. Results indicated that negative affect reactivity partially mediated personality and physical health. Wave 1 neuroticism was associated with greater negative affect reactivity at Wave 2, which predicted the development of chronic conditions and functional limitations at Wave 3. Higher conscientiousness at Wave 1 was associated with less negative affect reactivity at Wave 2, which predicted better physical health at Wave 3. These findings highlight the usefulness of using a daily-stress framework for understanding how personality impacts health over time, which has important implications for stress management and disease prevention.

The association between psychological functioning and social support and social constraint after cancer diagnosis: a 30-day daily diary study.

This study evaluated one positive and one negative aspect of social functioning (social support and social constraint, respectively) to increase understanding of its relation to psychological functioning (distress and wellbeing) after cancer diagnosis. Participants in this longitudinal study were recently diagnosed, predominately late stage, first primary cancer survivors (n = 48). Data collection involved a 30-day period of daily assessment. Data were analyzed using multilevel linear models. As in prior studies, none of the variables changed significantly over time (ps = .07 to .99). Based on the intraclass correlation coefficient, 51 to 75% of the variance in the daily assessment data are attributable to between-person differences. There was a positive relationship between social constraint and both general and cancer-specific distress (ps < .05) and between social support and cancer-specific wellbeing (ps < .001). In prospective models, higher than average general distress predicted higher social support the next day (p = .004) and higher than average cancer-specific wellbeing predicted more social constraint the next day (p = .01). The findings lend some support to the interdependence of social functioning and psychological functioning after cancer diagnosis.

A Qualitative Study of Smoking-Related Causal Attributions and Risk Perceptions in Cervical Cancer Survivors.

OBJECTIVE: The prevalence of smoking among cervical cancer survivors typically exceeds what is found among women in the general population and other cancer survivors. Yet, there is a dearth of literature on risk and protective factors related to smoking among cervical cancer survivors, especially when it comes to identification of variables that are amendable to intervention. To help fill this gap in the literature, this qualitative study examines the nature of smoking-related causal attributions and risk perceptions in cervical cancer survivors who smoked at cancer diagnosis. METHODS: Participants are 21 female cervical cancer survivors (M=45.7, SD=8.4 years old), all diagnosed in the past five years. Nearly three-quarters of participants reported smoking in the past month. RESULTS: Smoking was not uniformly recognized as a cause of cervical cancer (whether in general or participants' own cancer); the link between smoking and lung, head-neck, and other cancers was more readily accepted. Despite generally weak endorsements of causal attributions, many participants reported smoking significantly increases risk for poor clinical (e.g., recurrence) and quality of life (e.g., pain) outcomes after cervical cancer diagnosis. CONCLUSIONS: Findings suggest cervical cancer survivors may not fully understand or appreciate the role of smoking in cervical cancer risk whereas their beliefs about the role of smoking in cervical cancer prognosis are more well-formed. This study highlights the potential role of causal attributions and risk perceptions in understanding and addressing the smoking-related experience of cervical cancer survivors.

A Systematic Literature Review and Head-to-Head Comparison of Social Support and Social Constraint in Relation to the Psychological Functioning of Cancer Survivors.

BACKGROUND: Quality of life is a multidimensional concept that includes perceptions of one's physical, psychological, social, and spiritual functioning, all of which are theorized to be interdependent. The focus of this study is social functioning, which itself is a multidimensional concept that includes social support and social constraint among other things. In cancer survivors, social support receives most of the research attention, but social constraint may have a stronger influence on quality of life. PURPOSE: This systematic literature review evaluates which aspect of social functioning-social support or social constraint-has a stronger relationship with the psychological functioning of cancer survivors. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed in the identification and review of 32 independent records. Multiple measures of social support and social constraint were used across studies, with most having adequate psychometric properties. Psychological outcomes were divided into (a) general distress, (b) cancer-specific distress, (c) general well-being, and (d) cancer-specific well-being. RESULTS: For general and cancer-specific distress, social constraint exhibited a larger association with distress than social support. Similarly, for general well-being, most studies reported a stronger association with social constraint than social support. For cancer-specific well-being, the opposite was true such that associations were stronger for social support than social constraint. CONCLUSIONS: Results highlight the importance of considering social constraint when examining quality-of-life outcomes like psychological distress and well-being. Findings support social constraint as a target in interventions to reduce cancer survivors' distress, while social support could be considered in attempts to promote cancer-specific well-being.

The importance of using multiple outcome measures in infant research.

Collecting data with infants is notoriously difficult. As a result, many of our studies consist of small samples, with only a single measure, in a single age group, at a single time point. With renewed calls for greater academic rigor in data collection practices, using multiple outcome measures in infant research is one way to increase rigor, and, at the same time, enable us to more accurately interpret our data. Here, we illustrate the importance of using multiple measures in psychological research with examples from our own work on rapid threat detection and from the broader infancy literature. First, we describe our initial studies using a single outcome measure, and how this strategy caused us to nearly miss a rich and complex story about attention biases for threat and their development. We demonstrate how using converging measures can help researchers make inferences about infant behavior, and how using additional measures allows us to more deeply examine the mechanisms that drive developmental change. Finally, we provide practical and statistical recommendations for how researchers can use multiple measures in future work.

Causal attributions and their impact on psychosocial functioning in head and neck cancer patient-caregiver dyads: a preliminary, longitudinal study.

PURPOSE: This longitudinal study explores causal attributions in newly diagnosed head/neck cancer (HNC) patients and their caregivers. METHODS: Perceptions of causal attributions and associated level of responsibility regarding each patient's HNC diagnosis at baseline (n = 72 dyads) were described and then tested as predictors of depressive symptoms, cancer worry, and perceived support 6 months later. RESULTS: When causes were reported, tobacco and alcohol use topped the list of both patients and caregivers. Three-quarters of dyads agreed about perceptions of the patients' responsibility in causing their HNC. Some dyad-level patterns of causal attribution were associated with patients' and caregivers' cancer worry (p < 0.05) and caregivers' perceived support (p < 0.05) in unadjusted models. CONCLUSIONS: This preliminary study indicates that causal attributions warrant further exploration in HNC patient-caregiver dyads specifically, as well as studies of quality of life in patient-caregiver dyads more broadly considered.

Crohn's and Colitis Foundation of America Partners Patient-Powered Research Network: Patient Perspectives on Facilitators and Barriers to Building an Impactful Patient-Powered Research Network.

BACKGROUND: To build a Patient-Powered Research Networks (PPRN) that prioritizes the needs of its members who have inflammatory bowel diseases (IBD), we sought to better understand patients' preferences for what are the essential features that will facilitate and sustain engagement. METHODS: We conducted a two-phase qualitative study. Seven focus groups involving 62 participants with IBD were conducted (phase 1). Focus group results informed the phase 2 cognitive interviews, which included 13 phone interviews. Topics included experiences with IBD and research, PPRN engagement, patient-generated health data, and resources/tools to facilitate self-management. All focus groups and interviews were digitally recorded, transcribed verbatim, and analyzed in ATLAS.ti 7.5. Thematic categories were derived from the data, and codes were grouped into emergent themes and relationships. RESULTS: Four major themes emerged through inductive coding: (1) the impact of knowing; (2) participation barriers and challenges; (3) engagement and collaboration; and (4) customizable patient portal features/functionalities. Participants were motivated to participate in the PPRN because the knowledge gained from research studies would benefit both society and the individual. Main concerns included credibility of online resources, pharmaceutical industry profiting from their data, data security, and participation expectations. Participants wanted a true and equal partnership in every phase of building a PPRN. Participants felt it was important to have access to personal health records and be able to track health status and symptoms. CONCLUSION: Partnering with participants throughout PPRN development was critical to understanding the needs and preferences of patients with IBDs and for shaping engagement strategies and the portal's design.

Perceptions of Snus Among US Adult Smokers Given Free Product.

INTRODUCTION: Snus uptake is nominal among US smokers. This longitudinal study examines (1) perceptions of snus among US smokers given free snus for 6 weeks and (2) a method for assessment of an alternative tobacco product at the population level. METHODS: Adult smokers (n = 543; 69.2% female; Mage = 49.3 years), uninterested in quitting, received free snus for ad libitum use. Based on their snus use during a 6-week sampling period, participants included: (1) never users (18.4%, n = 100); (2) experimenters; that is, used ≥ once, but not during the last week of sampling (33.1%; n = 180); and (3) persistent users; that is, used ≥ once during the final week, and ≥ once during any other week of the sampling period. (48.4%; n = 263). RESULTS: Following the sampling period, those who became persistent users were more likely than experimenters to report that switching to alternative tobacco products would lower their risk for health problems (66.5% vs. 50.0%; p = .006). Persistent users also reported greater negative affect relief and craving reduction (ps < .001) than experimenters. Finally, persistent users were more likely than experimenters to describe snus in favorable terms with respect to ease of use, satisfaction, and liking (ps < .05). CONCLUSIONS: Subjective experiences with snus, rather than nicotine dependence, explained experimentation versus persistent use. Even among smokers who became persistent snus users, snus was perceived as a poor substitute for cigarettes. This study design (randomized, yet naturalistic) could be extended to other novel tobacco products, including e-cigarettes, to help understand the role new products may have in the tobacco landscape. IMPLICATIONS: This is the first large scale, US-based naturalistic assessment of smokers' reactions to snus during an extended sampling period. This study is directly in line with FDA goals to better understand predictors of initiation, uptake, and use of other tobacco products such as snus, and serves as model for assessment methods of alternative tobacco products at the population level. Most smokers tried the provided sample of snus (approximately 82%). Subjective experiences with snus, rather than nicotine dependence, explained experimentation versus persistent use. Even among smokers who became persistent snus users, snus was perceived as a poor substitute for cigarettes.

Snus undermines quit attempts but not abstinence: a randomised clinical trial among US smokers.

BACKGROUND: Observational studies and a few clinical trials suggest that use of low nitrosamine smokeless tobacco (snus) can facilitate smoking cessation. To better understand the real-world impact of snus on smoking behaviour, a large-scale, long-term clinical trial of naturalistic snus use among smokers is needed. STUDY DESIGN: A nationwide clinical trial compared abstinence outcomes among smokers who were randomised to receive free samples of snus versus not. Participants (N=1236) were recruited throughout the US and assessed for 1 year following a 6-week naturalistic sampling period, with high retention throughout. Primary outcomes included self-reported quit attempts, floating abstinence (any 7-day period of non-smoking) and 7-day point-prevalence abstinence at 6 months and 12 months. Secondary outcomes were changes in smoking, motivation and confidence to quit and adverse events. No tobacco industry support was provided. RESULTS: Within snus group, 82% used at least once, and 16% were using regularly at end of sampling period. Compared to control participants, smokers in the snus group were less likely to make any quit attempt (RR=0.83; 95% CI 0.70 to 1.00), and any 24 h quit attempt (RR=0.77; 95% CI 0.63 to 0.95). There were no group differences on any measure of abstinence. CONCLUSIONS: Provision of snus in a naturalistic context resulted in minimal uptake, and as a whole, undermined quit attempts and did not increase smoking abstinence. Results do not support the unguided, free provision of snus among smokers not motivated to quit as a means to facilitate quit attempts. TRIAL REGISTRATION NUMBER: NCT01509586, Results.

Fear-specific amygdala function in children and adolescents on the fragile x spectrum: a dosage response of the FMR1 gene.

Mutations of the fragile X mental retardation 1 (FMR1) gene are the genetic cause of fragile X syndrome (FXS). The presence of significant socioemotional problems has been well documented in FXS although the brain basis of those deficits remains unspecified. Here, we investigated amygdala dysfunction and its relation to socioemotional deficits and FMR1 gene expression in children and adolescents on the FX spectrum (i.e., individuals whose trinucleotide CGG repeat expansion from 55 to over 200 places them somewhere within the fragile X diagnostic range from premutation to full mutation). Participants performed an fMRI task in which they viewed fearful, happy, and scrambled faces. Neuroimaging results demonstrated that FX participants revealed significantly attenuated amygdala activation in Fearful > Scrambled and Fearful > Happy contrasts compared with their neurotypical counterparts, while showing no differences in amygdala volume. Furthermore, we found significant relationships between FMR1 gene expression, anxiety/social dysfunction scores, and reduced amygdala activation in the FX group. In conclusion, we report novel evidence regarding a dosage response of the FMR1 gene on fear-specific functions of the amygdala, which is associated with socioemotional deficits in FXS.