Prevalence of Sexual Violence and Intimate Partner Violence Among US Military Veterans: Findings from Surveys with Two National Samples.

BACKGROUND: Sexual violence (SV) and intimate partner violence (IPV) experiences are major social determinants of adverse health. There is limited prevalence data on these experiences for veterans, particularly across sociodemographic groups. OBJECTIVE: To estimate the prevalence of SV before, during, and after military service and lifetime and past-year IPV for women and men, and explore differences across sociodemographic groups. DESIGN: Data are from two national cross-sectional surveys conducted in 2020. Weighted prevalence estimates of SV and IPV experiences were computed, and weighted logistic regression models were used for comparisons across gender, race, ethnicity, sexual orientation, and age. PARTICIPANTS: Study 1 included veterans of all service eras (N = 1187; 50.0% women; 29% response rate). Study 2 included recently separated post-9/11 veterans (N = 1494; 55.2% women; 19.4% response rate). MAIN MEASURES: SV was assessed with the Deployment Risk and Resilience Inventory-2 (DRRI-2). IPV was assessed with the extended Hurt-Insult-Threaten-Scream Tool. KEY RESULTS: Women were more likely than men to experience pre-military SV (study 1: 39.9% vs. 8.7%, OR = 6.96, CIs: 4.71-10.28; study 2: 36.2% vs. 8.6%, OR = 6.04, CIs: 4.18-8.71), sexual harassment and/or assault during military service (study 1: 55.0% vs. 16.8%, OR = 6.30, CIs: 4.57-8.58; study 2: 52.9% vs. 26.9%, OR = 3.08, CIs: 2.38-3.98), and post-military SV (study 1: 12.4% vs. 0.9%, OR = 15.49, CIs: 6.42-36.97; study 2: 7.5% vs. 1.5%, OR = 5.20, CIs: 2.26-11.99). Women were more likely than men to experience lifetime IPV (study 1: 45.7% vs. 37.1%, OR = 1.38, CIs: 1.04-1.82; study 2: 45.4% and 34.8%, OR = 1.60, CIs: 1.25-2.04) but not past-year IPV (study 1: 27.9% vs. 28.3%, OR = 0.95, CIs: 0.70-1.28; study 2: 33.1% vs. 28.5%, OR = 1.24, CIs: 0.95-1.61). When controlling for gender, there were few differences across other sociodemographic groups, with the exception of sexual orientation. CONCLUSIONS: Understanding veterans' experiences of SV and IPV can inform identification and intervention efforts, especially for women and sexual minorities.

What next for eating disorder genetics? Replacing myths with facts to sharpen our understanding.

Substantial progress has been made in the understanding of anorexia nervosa (AN) and eating disorder (ED) genetics through the efforts of large-scale collaborative consortia, yielding the first genome-wide significant loci, AN-associated genes, and insights into metabo-psychiatric underpinnings of the disorders. However, the translatability, generalizability, and reach of these insights are hampered by an overly narrow focus in our research. In particular, stereotypes, myths, assumptions and misconceptions have resulted in incomplete or incorrect understandings of ED presentations and trajectories, and exclusion of certain patient groups from our studies. In this review, we aim to counteract these historical imbalances. Taking as our starting point the Academy for Eating Disorders (AED) Truth #5 "Eating disorders affect people of all genders, ages, races, ethnicities, body shapes and weights, sexual orientations, and socioeconomic statuses", we discuss what we do and do not know about the genetic underpinnings of EDs among people in each of these groups, and suggest strategies to design more inclusive studies. In the second half of our review, we outline broad strategic goals whereby ED researchers can expand the diversity, insights, and clinical translatability of their studies.

The impact of the COVID-19 pandemic on eating disorders in U.S. military veterans.

PURPOSE: The COVID-19 pandemic has had a profound impact on mental health around the world. Although there have been reports that the incidence of eating disorders (EDs) has increased during the pandemic, few longitudinal studies have examined recent changes in EDs. Men and women with military histories may be particularly vulnerable to EDs, underscoring the importance of investigating the impact of the COVID-19 pandemic on EDs in this population. METHOD: We examined whether early-pandemic (Time 1; T1) posttraumatic stress disorder, depression, anxiety, and stress symptoms were associated with change in probable ED diagnostic status 1 year later (T2). We also investigated relationships from early pandemic mental health symptoms to change in ED diagnostic status from T1 to T2 via pandemic-related life circumstance pathways (health, financial, social, etc.). Participants included a population-based sample of 372 U.S. veterans who completed the T1 and T2 surveys. RESULTS: Early pandemic mental health was significantly and positively associated with probable ED diagnostic status. Social and health satisfaction as well as physical health pandemic impacts mediated the associations between mental health symptoms and ED diagnostic status. DISCUSSION: Findings highlight the importance of bolstering social connection, health-promoting behaviors, and access to ED treatment among veteran men and women impacted by the COVID-19 pandemic. PUBLIC SIGNIFICANCE: The COVID-19 pandemic has had a profound impact on mental health, including eating disorders (EDs). We found that early pandemic mental health symptoms were significantly associated with changes in U.S. veterans' ED diagnostic status 1 year later. Mental health symptoms increased ED diagnoses via their impact on social and health satisfaction, as well as physical health impacts of the pandemic. Findings highlight the importance of increasing social connection, health-promoting behaviors, and ED treatment access among veteran men and women, who may be particularly vulnerable to EDs, during the COVID pandemic.

Associations between DSM-5 posttraumatic stress disorder Criterion E2 endorsement and selected self-destructive behaviors in recent-era veterans: A focus on disordered eating.

Revisions to the posttraumatic stress disorder (PTSD) criteria in the DSM-5 included a new criterion in the alterations in arousal and reactivity cluster (i.e., engagement in reckless and self-destructive behaviors; Criterion E2). Despite its clinical significance, little is known about how this symptom corresponds to engagement in specific direct and indirect self-harm behaviors. We examined associations between E2 and self-reported recent engagement in direct and indirect self-harm behaviors, including disordered eating, which is not included in the prototypical E2 symptom scope, in a trauma-exposed sample of 1,010 recent-era veterans (61.5% self-identified women, 38.5% self-identified men). We also tested whether gender moderated these associations. We repeated analyses in a subsample of participants with clinically elevated PTSD symptoms. Participants self-reported past-month PTSD symptoms (PCL-5) as well as past-month nonsuicidal self-injury, suicidal ideation, suicide planning, fasting, purging, binge eating, compulsive exercise, and problematic alcohol and drug use. We found no evidence for moderation by gender for any of the behaviors examined in the main sample. However, after controlling for gender and demographic covariates, weighted logistic regressions showed small, significant associations between E2 score and direct self-harm behaviors, substance use, purging, and binge eating, aORs = 1.30-1.91. Criterion E2 was linked to behaviors included in the typical symptom scope (self-directed violence, substance use) and those that are not (disordered eating behaviors). Comprehensive screening for self-destructive behaviors, including disordered eating, among veteran men and women who endorse Criterion E2 is indicated.

Effects of Intimate Partner Violence During COVID-19 and Pandemic-Related Stress on the Mental and Physical Health of Women Veterans.

BACKGROUND: Little is known about women veterans' intimate partner violence (IPV) experiences during the COVID-19 pandemic or the impacts of pandemic-related stress on their mental and physical health. OBJECTIVES: To identify IPV experiences among women veterans prior to and during the pandemic, pandemic-related stressors, and examine their respective contributions to mental and physical health. DESIGN: National sample of women veterans drawn from a larger web-based longitudinal study. Relationships between recent IPV and pandemic-related stressors were tested with linear regressions, controlling for pre-pandemic IPV and mental and physical health symptoms, demographic, and military-related covariates. PARTICIPANTS: One hundred forty-two women veterans (Mage=58.8 years). MAIN MEASURES: We assessed IPV (CTS-2), PTSD (PCL-5), depression (CESD), anxiety (DASS-A), physical health (PHQ-15), and physical health-related quality of life (SF-12) prior to the pandemic (June 2016-December 2016/January 2017) and during the pandemic study period (March 2020-December 2020/January 2021). We assessed pandemic-related stressors (EPII) during the pandemic study period. KEY RESULTS: Over a third (38.7%) of participants experienced IPV during the pandemic study period (psychological: 35.9%, physical: 9.9%, sexual: 4.2%). Overall rates, frequency, and severity of IPV experience did not significantly differ between the pre-pandemic and pandemic study periods. Few participants tested positive for COVID-19 (4.2%); however, most participants reported experiencing pandemic-related stressors across life domains (e.g., social activities: 88%, physical health: 80.3%, emotional health: 68.3%). IPV during the pandemic and pandemic-related stressors were both associated with greater PTSD and depressive symptoms. Pandemic-related stressors were associated with worse anxiety and physical health symptoms. Neither IPV during the pandemic nor pandemic-related stressors were associated with physical health-related quality of life. CONCLUSIONS: IPV experiences during the pandemic were common among women veterans, as were pandemic-related stressors. Although IPV did not increase in the context of COVID-19, IPV experiences during the pandemic and pandemic-related stressors were linked with poorer mental and physical health.

Disordered eating in sexual minority post-9/11 United States veterans.

OBJECTIVE: It is well documented that sexual minority individuals are more likely to report disordered eating (DE) than those identifying as heterosexual. Although DE is prevalent in veterans, investigation of potential disparities in DE among sexual minority veterans is limited. This study examined rates of DE in post-9/11 United States (U.S.) veterans identifying as sexual minorities and explored their association with discrimination because of marginalized identities. METHODS: A national sample of recently separated post-9/11 U.S. veterans were recruited. Women (N = 805; heterosexual [n = 656]; lesbian [n = 51]; bisexual [n = 98]) and men (N = 558; heterosexual [n = 540]; gay [n = 11]; bisexual [n = 7]) completed a survey assessing eating behaviors, mental health, and military experiences. Weighted correlational and regression analyses were conducted. Analyses in men were exploratory. RESULTS: DE was prevalent across gender and sexual orientation identity groups. Women identifying as bisexual and men identifying as gay reported higher rates of DE and consequent impairment compared to veterans who identified as heterosexual. There were no differences in DE between heterosexual and lesbian female veterans, but lesbian women reported lower DE-related impairment. Experiencing any discrimination in the military was positively related to DE. DISCUSSION: This study found evidence of disparities in DE among sexual minority U.S. military veterans. While the factors contributing to these differences, such as the role of discrimination, are not completely understood, DE is a health concern for sexual minority veterans and requires continued investigation. PUBLIC SIGNIFICANCE: Sexual minority individuals experience disparities in disordered eating; yet, this has not been explored in military veterans. This study found that disordered eating is a significant health concerns for veteran women and men, especially among those identifying as sexual minorities. More research is needed to explore why these disparities exist, such as the role of minority stress, in order to address the unique healthcare needs of these veterans.

Latent Class Analysis of Self-directed Violence and Indirect Self-harm Behaviors: Gender Differences and Associations With Mental Health Symptoms.

OBJECTIVE: This study aimed to (1) examine whether the latent class structure of individuals engaging in self-directed violence and indirect self-harm behaviors (eg, substance use, disordered eating) varied by gender in a sample of US veterans, and (2) test the associations of posttraumatic stress disorder (PTSD) and depressive symptoms with the resulting classes. STUDY DESIGN: Cross-sectional data from 3581 veterans, ages 18-50 (51.9% identified as women) were analyzed. Veterans self-reported histories of self-directed violence, substance use, and disordered eating. Latent class analysis and latent class regression were used to explore class structure by gender and examine association of class membership with PTSD and depressive symptoms. RESULTS: A 4-class model was supported in the sample. Class 1 (20.0%) was characterized by substance use and self-directed violent thoughts and behaviors. Class 2 (8.3%) was characterized by substance use, disordered eating, and self-directed violent thoughts and behaviors. Class 3 (12.6%) was distinguished by indirect self-harm behaviors (substance use and disordered eating). Class 4 (59.6%) reflected low likelihood of behavioral dysregulation. Classes were partially invariant across gender; endorsement of substance use behaviors was generally higher for men in each class. Comorbid clinically significant depressive and PTSD symptoms were associated with the class characterized by highest behavioral dysregulation. CONCLUSIONS: Self-directed violent thoughts and behaviors present comorbidly with indirect self-harm in men and women veterans, although patterns of indirect self-harm behaviors differ slightly by gender. Such comorbidity may be associated with more severe presentations of psychiatric concerns.

The impact of comorbid posttraumatic stress disorder on eating disorder treatment outcomes: Investigating the unified treatment model.

PURPOSE: Many women with eating disorders (EDs) have comorbid posttraumatic stress disorder (PTSD). However, there have been few studies on how comorbid PTSD may impact ED treatment outcomes. METHOD: Participants were 2,809 patients from residential ED treatment facilities who were treated using the Unified Treatment Model (UTM). We investigated whether PTSD diagnosis at admission was associated with changes in Eating Disorder Examination-Questionnaire (EDE-Q) scores, binge eating, self-induced vomiting, and restriction, across three time points, as well as clinically significant improvement and treatment drop-out. RESULTS: Using latent growth models, with time modeled as a second-order polynomial, we found that EDE-Q scores and behavioral symptoms decreased from admission to discharge, but increased from discharge to 6-month follow-up. PTSD diagnosis was associated with higher baseline EDE-Q scores and restriction, and lower binge-eating frequency. PTSD diagnosis was not associated with symptom change over time, treatment dropout, or clinically significant change. DISCUSSION: Although PTSD diagnoses were associated with higher ED symptom levels at admission, PTSD was not associated with worse treatment outcomes, suggesting the UTM is a promising treatment for patients with and without PTSD. Future studies should investigate the impact of ED treatment on PTSD symptoms in order to determine the need for integrated treatments for these comorbid conditions.

Posttraumatic stress disorder and eating disorders: maintaining mechanisms and treatment targets.

Many individuals with lifetime histories of eating disorders (EDs) report exposure to interpersonal trauma and posttraumatic stress disorder (PTSD). However, this relationship is not well-understood, and there are no established, evidence-based therapies for the concurrent treatment of EDs and PTSD. This review focuses on studies of the mechanisms associating trauma exposure and/or PTSD with EDs. Possible mechanisms of the trauma-ED association identified from the literature include self-criticism, low self-worth, guilt, shame, depression, anxiety, emotion dysregulation, anger, and impulsivity/compulsivity. ED behaviors may be used as coping strategies to manage PTSD symptoms and negative affect. Avoidance of hyperarousal symptoms by engaging in binge eating, purging, and/or restriction may serve to maintain both the ED as well as the PTSD. Given the evidence of the bidirectional relationship between EDs and PTSD, we describe an integrated cognitive behavioral theory that may account for the persistence of comorbid PTSD and EDs. The integrated model is based on the theoretical models that underpin existing evidence-based treatments for PTSD and ED and incorporates many of the potential mechanisms highlighted to date. The primary aim of the model is to identify potential treatment targets as well as elucidate future directions for research.

Non-muscle myosin IIB (Myh10) is required for epicardial function and coronary vessel formation during mammalian development.

The coronary vasculature is an essential vessel network providing the blood supply to the heart. Disruptions in coronary blood flow contribute to cardiac disease, a major cause of premature death worldwide. The generation of treatments for cardiovascular disease will be aided by a deeper understanding of the developmental processes that underpin coronary vessel formation. From an ENU mutagenesis screen, we have isolated a mouse mutant displaying embryonic hydrocephalus and cardiac defects (EHC). Positional cloning and candidate gene analysis revealed that the EHC phenotype results from a point mutation in a splice donor site of the Myh10 gene, which encodes NMHC IIB. Complementation testing confirmed that the Myh10 mutation causes the EHC phenotype. Characterisation of the EHC cardiac defects revealed abnormalities in myocardial development, consistent with observations from previously generated NMHC IIB null mouse lines. Analysis of the EHC mutant hearts also identified defects in the formation of the coronary vasculature. We attribute the coronary vessel abnormalities to defective epicardial cell function, as the EHC epicardium displays an abnormal cell morphology, reduced capacity to undergo epithelial-mesenchymal transition (EMT), and impaired migration of epicardial-derived cells (EPDCs) into the myocardium. Our studies on the EHC mutant demonstrate a requirement for NMHC IIB in epicardial function and coronary vessel formation, highlighting the importance of this protein in cardiac development and ultimately, embryonic survival.

p63 exerts spatio-temporal control of palatal epithelial cell fate to prevent cleft palate.

Cleft palate is a common congenital disorder that affects up to 1 in 2500 live births and results in considerable morbidity to affected individuals and their families. The aetiology of cleft palate is complex with both genetic and environmental factors implicated. Mutations in the transcription factor p63 are one of the major individual causes of cleft palate; however, the gene regulatory networks in which p63 functions remain only partially characterized. Our findings demonstrate that p63 functions as an essential regulatory molecule in the spatio-temporal control of palatal epithelial cell fate to ensure appropriate fusion of the palatal shelves. Initially, p63 induces periderm formation and controls its subsequent maintenance to prevent premature adhesion between adhesion-competent, intra-oral epithelia. Subsequently, TGFß3-induced down-regulation of p63 in the medial edge epithelia of the palatal shelves is a pre-requisite for palatal fusion by facilitating periderm migration from, and reducing the proliferative potential of, the midline epithelial seam thereby preventing cleft palate.

A classical twin study of PTSD symptoms and resilience: Evidence for a single spectrum of vulnerability to traumatic stress.

BACKGROUND: To examine shared genetic and environmental risk factors across PTSD symptoms and resilience. METHODS: Classical twin study of 2010-2012 survey data conducted among 3,318 male twin pairs in the Vietnam Era Twin Registry. Analyses included: (a) estimates of genetic and environmental influences on PTSD symptom severity (as measured by the PTSD Checklist) and resilience (assessed with the Connor-Davidson Resilience Scale-10); (b) development of a latent model of traumatic stress, spanning both PTSD and resilience; and (c) estimates of genetic and environmental influences on this spectrum. RESULTS: The heritability of PTSD was 49% and of resilience was 25%. PTSD and resilience were correlated at r = -.59, and 59% of this correlation was attributable to a single genetic factor, whereas the remainder was due to a single non-shared environment factor. Resilience was also influenced by common and unique environmental factors not shared with PTSD, but there was no genetic factor specific to resilience. Confirmatory factor analysis supported the Development of a revised phenotype reflecting the broader dimension of traumatic stress, with biometric models suggesting increased heritability (66%) of this spectrum compared to PTSD or resilience individually. CONCLUSIONS: Genetic factors contribute to a single spectrum of traumatic stress reflecting resilience at one end and high symptom severity at the other. This carries implications for phenotype refinement in the search for molecular genetic markers of trauma-related psychopathology. Rather than focusing only on genetic risk for PTSD, molecular genetics research may benefit from evaluation of the broader spectrum of traumatic stress.

Military-related trauma is associated with eating disorder symptoms in male veterans.

OBJECTIVE: Eating disorders are understudied among male veterans, who may be at increased risk due to the high rates of trauma exposure and experiences of multiple traumatization in this population. This study sought to examine the associations between specific types of trauma (i.e., childhood physical abuse, adult physical assault, childhood sexual abuse, adult sexual assault, and military-related trauma) and eating disorder symptoms in a large, nationally-representative sample of trauma-exposed male veterans. METHOD: Survey data were collected from N = 642 male veterans. Traumatic experiences in childhood and adulthood were assessed using the Trauma History Screen and the National Stressful Events Survey. Eating disorder symptoms were assessed with the Eating Disorder Diagnostic Scale. Analyses also controlled for age and body mass index. RESULTS: Multiple traumatization was associated with increased eating disorder symptoms. However, military-related trauma was the only trauma type that was uniquely associated with eating disorder symptoms when controlling for other trauma types. Examination of different types of military-related trauma indicated that this association was not driven by exposure to combat. DISCUSSION: Noncombat, military-related trauma was associated with eating disorder symptom severity in male veterans. Results highlight the need for better assessment of eating disorder symptoms in this population.

Source memory that encoding was self-referential: the influence of stimulus characteristics.

Decades of research suggest that encoding information with respect to the self improves memory (self-reference effect, SRE) for items (item SRE). The current study focused on how processing information in reference to the self affects source memory for whether an item was self-referentially processed (a source SRE). Participants self-referentially or non-self-referentially encoded words (Experiment 1) or pictures (Experiment 2) that varied in valence (positive, negative, neutral). Relative to non-self-referential processing, self-referential processing enhanced item recognition for all stimulus types (an item SRE), but it only enhanced source memory for positive words (a source SRE). In fact, source memory for negative and neutral pictures was worse for items processed self-referentially than non-self-referentially. Together, the results suggest that item SRE and source SRE (e.g., remembering an item was encoded self-referentially) are not necessarily the same across stimulus types (e.g., words, pictures; positive, negative). While an item SRE may depend on the overall likelihood the item generates any association, the enhancing effects of self-referential processing on source memory for self-referential encoding may depend on how embedded a stimulus becomes in one's self-schema, and that depends, in part, on the stimulus' valence and format. Self-relevance ratings during encoding provide converging evidence for this interpretation.

Examining weight and eating behavior by sexual orientation in a sample of male veterans.

OBJECTIVE: Eating disorders are understudied in men and in sexual minority populations; however, extant evidence suggests that gay men have higher rates of disordered eating than heterosexual men. The present study examined the associations between sexual orientation, body mass index (BMI), disordered eating behaviors, and food addiction in a sample of male veterans. METHOD: Participants included 642 male veterans from the Knowledge Networks-GfK Research Panel. They were randomly selected from a larger study based on previously reported trauma exposure; 96% identified as heterosexual. Measures included the Eating Disorder Diagnostic Scale, the Yale Food Addiction Scale, and self-reported height and weight. RESULTS: Heterosexual and sexual minority men did not differ significantly in terms of BMI. However, gay and bisexual men (n=24) endorsed significantly greater eating disorder symptoms and food addiction compared to heterosexual men. CONCLUSIONS: Our findings that sexual minority male veterans may be more likely to experience eating disorder and food addiction symptoms compared to heterosexual male veterans highlight the importance of prevention, assessment, and treatment efforts targeted to this population.

Exome sequence identifies RIPK4 as the Bartsocas-Papas syndrome locus.

Pterygium syndromes are complex congenital disorders that encompass several distinct clinical conditions characterized by multiple skin webs affecting the flexural surfaces often accompanied by craniofacial anomalies. In severe forms, such as in the autosomal-recessive Bartsocas-Papas syndrome, early lethality is common, complicating the identification of causative mutations. Using exome sequencing in a consanguineous family, we identified the homozygous mutation c.1127C>A in exon 7 of RIPK4 that resulted in the introduction of the nonsense mutation p.Ser376X into the encoded ankyrin repeat-containing kinase, a protein that is essential for keratinocyte differentiation. Subsequently, we identified a second mutation in exon 2 of RIPK4 (c.242T>A) that resulted in the missense variant p.Ile81Asn in the kinase domain of the protein. We have further demonstrated that RIPK4 is a direct transcriptional target of the protein p63, a master regulator of stratified epithelial development, which acts as a nodal point in the cascade of molecular events that prevent pterygium syndromes.

Age-related differences in the neural basis of the subjective vividness of memories: evidence from multivoxel pattern classification.

Although older adults often show reduced episodic memory accuracy, their ratings of the subjective vividness of their memories often equal or even exceed those of young adults. Such findings suggest that young and older adults may differentially access and/or weight different kinds of information in making vividness judgments. We examined this idea using multivoxel pattern classification of fMRI data to measure category representations while participants saw and remembered pictures of objects and scenes. Consistent with our hypothesis, there were age-related differences in how category representations related to the subjective sense of vividness. During remembering, older adults' vividness ratings were more related, relative to young adults', to category representations in prefrontal cortex. In contrast, young adults' vividness ratings were more related, relative to older adults, to category representations in parietal cortex. In addition, category representations were more correlated among posterior regions in young than in older adults, whereas correlations between PFC and posterior regions did not differ between the 2 groups. Together, these results are consistent with the idea that young and older adults differentially weight different types of information in assessing subjective vividness of their memories.

p63-dependent and independent mechanisms of nectin-1 and nectin-4 regulation in the epidermis.

Nectins are immunoglobulin-like cell adhesion molecules mainly localized in adherens junctions. The transcription factor p63 is a master regulator of gene expression in stratified epithelia and controls several molecular processes. As mutations in the Pvrl1 and Pvrl4 genes encoding for nectins cause genetic disorders with phenotypes similar to p63-related syndromes, we investigated whether these proteins might be under p63 transcriptional control. Here, we show that in p63-null skin, Pvrl1 gene expression is strongly reduced, whereas Pvrl4 expression is unaffected. In human and mouse primary keratinocytes p63 depletion leads to a specific downregulation of the Pvrl1 gene. Consistent with a direct regulation, chromatin immunoprecipitation experiments (ChIP) indicate that p63 binds to two conserved intronic Pvrl1 enhancer regions. Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome is a rare autosomal dominant disorder, caused by mutations in p63 gene, mainly characterized by skin fragility. To test whether nectins may be affected in AEC syndrome, their expression was measured in keratinocytes obtained from patients with AEC or from a conditional mouse model for AEC syndrome. Pvrl1 expression was reduced in AEC keratinocytes, consistent with impaired p63 function. Surprisingly, Pvrl4 expression was similarly affected, in parallel with decreased expression of the transcription factor Irf6. Consistent with the well-characterized role of Irf6 in keratinocyte differentiation and its strong downregulation in AEC syndrome, Irf6 depletion caused reduced expression of Pvrl4 in wild-type keratinocytes. Taken together, our results indicate that Pvrl1 is a bona fide target gene of the transcription factor p63, whereas Pvrl4 regulation is linked to epidermal differentiation and is under Irf6 control.