Cognitive Flexibility and Impulsivity Deficits in Suicidal Adolescents.

Although neurocognitive deficits have been documented in adolescents with suicidal ideation (SI) and suicide attempts (SA), it is unclear whether certain impairments differentiate these groups, potentially suggesting heightened risk for SA. Focus on specific facets of impulsivity and cognitive control may indicate distinctions between adolescents with SA vs. SI. The current study examined dimensions of impulsivity and cognitive control in 141 adolescents with SA (n = 41) vs. SI without SA (n = 49) vs. typically-developing controls (TDCs; n = 51). Adolescents completed cross-sectional neurocognitive tasks via the Cambridge Neuropsychological Testing Automated Battery, in addition to demographic and clinical measures. Analyses involved ANOVAs and ANCOVAs. Results indicated that adolescents with SA demonstrated less set shifting/cognitive flexibility (reduced ability to adapt to/disengage from stimuli) and greater impulsive decision making (reduced ability to collect/evaluate information before making decisions) compared to TDCs. In addition, both TDCs and adolescents with SA had greater response inhibition (increased ability to stop motor responses that have begun/become prepotent) than those with SI. Similar results were found when analyzing female adolescents separately. There were no significant differences for male adolescents, potentially due to the small subsample (n = 40). There were no significant findings for spatial planning/problem solving or visuospatial working memory. Findings suggest: 1) less set shifting/cognitive flexibility and greater impulsive decision making for adolescents with SA vs. TDCs; and 2) greater response inhibition for TDCs and adolescents with SA vs. SI. Such information may be useful for improving risk assessments (adding neurocognitive tasks) and targeted treatments (incorporating cognitive remediation) for this impaired population.

Maltreatment history and reasons for self-injurious behavior among adolescents engaged in non-suicidal self-injury versus adolescents who attempted suicide.

OBJECTIVE: Self-injurious behavior (SIB) is a significant public health concern in the United States, especially among adolescents with histories of maltreatment. This study compared maltreatment characteristics and reasons for SIB between three homogenous samples of adolescents with either: (1) non-suicidal self-injury (NSSI); (2) suicide attempt/s (SA), and (3) typically developing controls (TDC). METHOD: Participants (N = 124) aged 13-17 years completed questionnaires about their maltreatment and SIB histories. RESULTS: Maltreatment rates were as follows: 90% NSSI group, 76% SA group, and 40% TDC group. Adolescents in the NSSI group reported significantly higher rates of emotional neglect compared to the SA group. Maltreated adolescents in the NSSI and SA groups reported the same top three SIB reasons: (1) get rid of bad feelings, (2) mental state at the time, and (3) problems with family. However, maltreated NSSI participants were significantly more likely to engage in SIB for emotion regulation reasons than maltreated SA participants, who were more likely to engage in SIB for interpersonal reasons. Physical neglect and physical abuse also arose as significant predictors of specific SIB reasons. CONCLUSIONS: Our findings help elucidate the maltreatment profiles and reasons for SIB among adolescents engaged in NSSI or SA. Specific maltreatment experiences may also influence the reasons why adolescents engaged in SIB.

Sex and age moderate the trajectory of guilt among children and adolescents with and without recent suicidal ideation.

We aimed to examine whether the trajectories of ecologically derived guilt differ among a transdiagnostic sample of youth with and without recent suicidal ideation and whether sex and age moderated this association. We assessed guilt 3 times a day over a 2-week period via ecological momentary assessment (EMA) technology in 102 children recruited from the community, outpatient, and inpatient settings. The average age of children was 10.95 y.o. (SD = 2.26, range 8-16) and the majority were male (54.9%) and White (76.5%). We found that the real-world guilt during a two-week EMA period was higher among youth with greater suicidal ideation severity in the past six months. Moreover, there was a significant moderating effect of sex and age on this association, such that the association between suicidal ideation severity and guilt was particularly strong among females compared to males and youth who were 10 years old or older. The findings were maintained when we adjusted for the relevant demographic and clinical characteristics, including age, minority status, parental income, EMA response rate, and current internalising symptoms. These preliminary findings highlight the clinical relevance of assessing and targeting feelings of guilt in the day-to-day lives of youth, particularly for females and older youth.

COVID-19-Specific Suicidal Thoughts and Behaviors in Psychiatrically Hospitalized Adolescents.

This study examined the presence and correlates of COVID-specific suicidal thoughts and behaviors (i.e., thoughts of or engaging in intentional COVID-19 exposure with associated suicidal intent) among psychiatrically hospitalized adolescents. Adolescents (N = 143) completed study measures as part of the standard intake process between March 13th and August 14th, 2020. Participants answered questionnaires assessing COVID-specific passive and active suicidal ideation (SI) and suicidal behavior, as well as COVID-related stressors and emotions, and public health guidance compliance. Findings highlights that COVID-specific SI is common in high-risk youth. COVID-specific SI was associated with COVID-19-related negative emotions, elevated stress, and decreased public health guidance compliance. Results suggest that COVID-specific suicidal thoughts and behaviors, and risk correlates, should be assessed within high-risk populations to facilitate prevention of risky behavior associated with intentional COVID-19 exposure.

Relationship between cognitive flexibility and subsequent course of mood symptoms and suicidal ideation in young adults with childhood-onset bipolar disorder.

Neurocognitive deficits, such as cognitive flexibility impairments, are common in bipolar disorder (BD) and predict poor academic, occupational, and functional outcomes. However, the association between neurocognition and illness trajectory is not well understood, especially across developmental transitions. This study examined cognitive flexibility and subsequent mood symptom and suicidal ideation (SI) course in young adults with childhood-onset BD-I (with distinct mood episodes) vs. BD-not otherwise specified (BD-NOS) vs. typically-developing controls (TDCs). Sample included 93 young adults (ages 18-30) with prospectively verified childhood-onset DSM-IV BD-I (n = 34) or BD-NOS (n = 15) and TDCs (n = 44). Participants completed cross-sectional neuropsychological tasks and clinical measures. Then participants with BD completed longitudinal assessments of mood symptoms and SI at 6-month intervals (M = 39.18 ± 16.57 months of follow-up data). Analyses included ANOVAs, independent-samples t tests, chi-square analyses, and multiple linear regressions. Participants with BD-I had significant deficits in cognitive flexibility and executive functioning vs. BD-NOS and TDCs, and impaired spatial working memory vs. TDCs only. Two significant BD subtype-by-cognitive flexibility interactions revealed that cognitive flexibility deficits were associated with subsequent percentage of time depressed and with SI in BD-I but not BD-NOS, regardless of other neurocognitive factors (full-scale IQ, executive functioning, spatial working memory) and clinical factors (current and prior mood and SI symptoms, age of BD onset, global functioning, psychiatric medications, comorbidity). Thus, cognitive flexibility may be an important etiological brain/behavior mechanism, prognostic indicator, and intervention target for childhood-onset BD-I, as this deficit appears to endure into young adulthood and is associated with worse prognosis for subsequent depression and SI.

COVID-19 Related Daily Stressors, Coping, and Suicidal Ideation in Psychiatrically Hospitalized Youth.

Background: Given reports of the adverse effects of COVID-19 on adolescent mental health, it is critical to understand how it impacts psychiatrically hospitalized youth who may be particularly vulnerable to its effects. Objective: This study aimed to advance our understanding of high-risk adolescents' experiences of COVID-19, including COVID-19-related stress, changes in daily functioning, and coping as they relate to suicidal ideation (SI). Method: Participants were 107 youth (ages 11-18; M = 15.06, SD = 1.79) admitted to an adolescent psychiatric inpatient unit during the time when the initial COVID-19 safety measures (i.e., school closure, stay-at-home- order) and reopening initiatives (Phase I, II, and III) were implemented in Rhode Island between March 13th and July 19th 2020. Adolescents completed measures of COVID-19-related stress, coping, functioning, and SI at the time of admission. Results: Nearly half of the sample (43%) reported a negative impact of COVID-19 on daily functioning. Youth who endorsed COVID-19-related decline in functioning evidenced higher levels of SI compared to youth with no change or improvement in functioning due to COVID-19. Overall levels of stress were not associated with SI. Greater coping repertoire, but not the use of specific coping strategies was associated with higher levels of SI. Conclusions: Findings demonstrate the importance of examining COVID-19-related changes in functioning and broadening repertoire of coping strategies among adolescents at high risk for SI. Supplementary Information: The online version contains supplementary material available at 10.1007/s10566-021-09641-1.

This Is Your Brain on Irritability: A Clinician's Guide to Understanding How We Know What We Know Now, and What We Need to Know in the Future, About Irritability in Children and Adolescents.

Irritability is a common reason why children and adolescents are brought for psychiatric care. Although research is advancing what is known about the underlying brain and behavior mechanisms of irritability, clinicians often are shut out of that research. This article explains some of these research methods, providing brief summaries of what is known about brain/behavior mechanisms in disorders involving irritability, including bipolar disorder, disruptive mood dysregulation disorder, attention-deficit/hyperactivity disorder, and autism spectrum disorder. Greater access to these methods may help clinicians now and in the future, with such mechanisms translated into improved care, as occurs in the treatment of childhood leukemia.

Social media use and self-injurious thoughts and behaviors: A systematic review and meta-analysis.

Despite considerable public and scholarly debate about the role of social media in self-injurious thoughts and behaviors (SITBs), no comprehensive, quantitative synthesis of this literature has previously been undertaken. The current systematic review and meta-analysis examines associations between social media use and SITBs, including suicidal ideation, suicide plans, suicide attempts, and nonsuicidal self-injury (NSSI). A range of social media behaviors and experiences were identified, including cybervictimization and perpetration, exposure to and generation of SITB-related content, problematic use, sexting, social media importance, and frequency of use. A systematic search of PsycINFO, Medline, CINAHL, and the references of prior reviews yielded 61 eligible studies. Results largely suggested medium effect sizes for associations between specific social media constructs (cybervictimization, SITB-related social media use, problematic social media use) and SITBs. There was no association between frequency of social media use and SITBs; however, studies on this topic were limited. The majority of studies identified focused on cybervictimization, and results suggested positive associations with all SITBs, with the association between cybervictimization and suicidal ideation stronger for adolescents than adults. Overall, findings highlight the utility of examining specific social media behaviors and experiences, and point to the need for more research in this area.

Facial emotion recognition and mood symptom course in young adults with childhood-onset bipolar disorder.

Facial emotion recognition deficits are common in bipolar disorder (BD) and associated with impairment. However, the relationship between facial emotion recognition and mood course is not well understood. This study examined facial emotion recognition and subsequent mood symptoms in young adults with childhood-onset BD versus typically developing controls (TDCs). The sample included 116 young adults (ages 18-30, 58% male, 78% White) with prospectively verified childhood-onset BD (n = 52) and TDCs (n = 64). At baseline, participants completed a facial emotion recognition task (Diagnostic Analysis of Non-Verbal Accuracy-2) and clinical measures. Then, participants with BD completed mood symptom assessments every 6 months (M = 8.7 ± 5.2 months) over two years. Analyses included independent-samples t tests and mixed-effects regression models. Participants with BD made significantly more recognition errors for child expressions than TDCs. There were no significant between-group differences for recognition errors for adult expressions, or errors for specific child or adult emotional expressions. Participants had moderate baseline mood symptoms. Significant time-by-facial emotion recognition interactions revealed more recognition errors for child emotional expressions predicted lower baseline mania and stable/consistent trajectory; fewer recognition errors for child expressions predicted higher baseline mania and decreasing trajectory. In addition, more recognition errors for adult sad expressions predicted stable/consistent depression trajectory and decreasing mania; fewer recognition errors for adult sad expressions predicted decreasing depression trajectory and stable/consistent mania. Effects remained when controlling for baseline demographics and clinical variables. Facial emotion recognition may be an important brain/behavior mechanism, prognostic indicator, and intervention target for childhood-onset BD, which endures into young adulthood and is associated with mood trajectory.

Parental Monitoring Predicts Depressive Symptom and Suicidal Ideation Outcomes in Adolescents Being Treated for Co-Occurring Substance Use and Psychiatric Disorders.

BACKGROUND: Comorbidity of substance use disorders (SUDs) with mood disorders and other psychiatric conditions is common. Parenting processes and family functioning are impaired in adolescents with SUDs and mood disorders, and parent/family factors predict intervention response. However, limited research has examined the relationship between parent/family factors and mood symptom treatment response in adolescents with comorbid SUDs and psychiatric conditions. METHOD: This study examined the predictive effects of parenting processes and family functioning on depressive symptoms and suicidal ideation (SI) in a randomized controlled trial of integrated cognitive-behavioral therapy vs. treatment as usual for 111 adolescents with comorbid SUDs and psychiatric disorders. Measures of parenting processes, family functioning, depressive symptoms, and SI were completed at baseline and 3-, 6-, and 12-month follow-ups. Exploratory analyses involved mixed-effects regression models. RESULTS: Across treatment conditions, depressive symptoms and SI improved over 12 months. Family functioning domains of family roles (d=0.47) and affective involvement (d=0.39) significantly improved across treatment conditions over 12 months. Higher baseline parental monitoring predicted improved trajectory of depressive symptoms (d=0.44) and SI (d=0.46). There were no significant predictive effects for baseline family functioning or other parenting processes (listening, limit setting). LIMITATIONS: Limitations include the modest sample, attrition over follow-up, and generalizability to samples with higher rates of mood disorders and/or uncomplicated mood disorders. CONCLUSIONS: Parental monitoring may be an important prognostic indicator of depressive symptoms and SI in adolescents with co-occurring SUDs and psychiatric conditions, and therefore may be useful to assess and target in treatment, in addition to family functioning.

Suicidal thoughts and behaviors in psychiatrically hospitalized adolescents pre- and post- COVID-19: A historical chart review and examination of contextual correlates.

BACKGROUND: Psychiatrically vulnerable adolescents may be at heightened risk for suicide during the COVID-19 pandemic. This study characterizes suicidal ideation (SI) and suicide attempts (SA) in a sample of adolescents psychiatrically hospitalized during COVID-19. Rates of SI and SA are compared to a historical hospital sample from a matched period in the year prior. Associations between specific stressors and COVID-related SI are also explored. METHODS: This cross-sectional chart review utilizes hospital intake data, including self-reports of SA, SI (general and COVID-related), and COVID-specific stressors. RESULTS: SA and SI ratings were higher in the COVID-19 sample compared to the historical sample. Stressors related to missing special events, financial problems, in-home conflict, and changes in living circumstances were associated with COVID-related SI. Among first-time admissions, several interpersonal stressors were linked to COVID-related SI. LIMITATIONS: Analyses were cross-sectional, limiting our ability to draw conclusions about causality. CONCLUSIONS: This study offers preliminary evidence that COVID-19 may be contributing to suicidal thoughts and behaviors in high-risk adolescents.

Online Self-Injury Activities among Psychiatrically Hospitalized Adolescents: Prevalence, Functions, and Perceived Consequences.

The majority of adolescents with psychiatric disorders use social media, engaging in a range of online activities that may confer both risks and benefits. Very little work, however, has examined engagement in online activities related to self-injury among these youth, such as posting about self-injury, viewing self-injury related content, or messaging about self-injury with online or offline friends. This study examined the frequency and types of online self-injury activities in which adolescents engage, perceived functions that these activities serve, and associated risk for self-injurious thoughts and behaviors (SITBs). Participants were 589 psychiatrically-hospitalized adolescents (Mage = 14.88), who completed self-report measures assessing online self-injury activities, perceived functions and consequences of these activities, and SITBs. Results indicated that 43.3% of the sample had engaged in online self-injury activities, that the majority (74.8%) used social networking sites (e.g., Snapchat, Instagram) to do so, and that these activities were significantly more common among sexual and gender minority youth. Adolescents who talked about self-injury with friends met online were more likely to report a history of suicide attempt(s). A latent profile analysis revealed three distinct subgroups of youth based on their perceived functions of engaging in online self-injury activities. Subgroups reporting higher levels of engagement for purposes of identity exploration, self-expression, and aiding recovery were at heightened risk for negative perceived consequences of these activities and reported greater suicidal ideation severity. Findings offer new insights for identifying youth who may be at heightened risk for SITBs in the context of social media use.

Maladaptive personality traits and the course of suicidal ideation in young adults with bipolar disorder: Cross-sectional and prospective approaches.

BACKGROUND: Childhood-onset bipolar disorder (BD) has considerable morbidity and mortality, including suicide. Many risk factors have been identified for suicidality, but the potential role of personality traits as assessed by a computer-assisted self-report measure remains unclear. AIMS: To address this gap in knowledge, we tested relations between pathological-range personality traits and suicidal ideation among young adults whose childhood-onset BD was prospectively confirmed by enrollment in the Course and Outcome of Bipolar Youth study (COBY) as children (n = 45) and a newly enrolled group of typically developing controls (TDCs; n = 52) both cross-sectionally and longitudinally after 1.5 years of follow up. MATERIALS & METHODS: Personality traits were assessed with the computerized Schedule for Nonadaptive and Adaptive Personality-2 (SNAP-2). RESULTS: Cross-sectionally, we found that participants with BD had elevated Suicide Proneness and Low Self-esteem versus TDCs at baseline. Furthermore, longitudinal analyses in the BD participants for whom we had 1.5 years of prospectively collected illness-course data showed that greater Suicide Proneness and Low Self-esteem prospectively predicted greater levels, shorter time until occurrence, and greater frequency of suicidal ideation during the follow-up. CONCLUSION: Our findings suggest the role of specific personality-related vulnerabilities in the course of BD that, pending replication, could contribute to development of interventions focused on personality traits among individuals with BD.

Clinician training, then what? Randomized clinical trial of child STEPs psychotherapy using lower-cost implementation supports with versus without expert consultation.

OBJECTIVE: Implementation of evidence-based treatments in funded trials is often supported by expert case consultation for clinicians; this may be financially and logistically difficult in clinical practice. Might less costly implementation support produce acceptable treatment fidelity and clinical outcomes? METHOD: To find out, we trained 42 community clinicians from four community clinics in Modular Approach to Therapy for Children (MATCH), then randomly assigned them to receive multiple lower-cost implementation supports (LC) or expert MATCH consultation plus lower-cost supports (CLC). Clinically referred youths (N = 200; ages 7-15 years, M = 10.73; 53.5% male; 32.5% White, 27.5% Black, 24.0% Latinx, 1.0% Asian, 13.5% multiracial, 1.5% other) were randomly assigned to LC (n = 101) or CLC (n = 99) clinicians, and groups were compared on MATCH adherence and competence, as well as on multiple clinical outcomes using standardized measures (e.g., Child Behavior Checklist, Youth Self-Report) and idiographic problem ratings (Top Problems Assessment). RESULTS: Coding of therapy sessions revealed substantial therapist adherence to MATCH in both conditions, with significantly stronger adherence in CLC; however, LC and CLC did not differ significantly in MATCH competence. Trajectories of change on all outcome measures were steep, positive, and highly similar for LC and CLC youths, with no significant differences; a supplemental analysis of posttreatment outcomes also showed similar LC and CLC posttreatment scores, with most LC-CLC differences nonsignificant. CONCLUSIONS: The findings suggest that effective implementation of a complex intervention in clinical practice may be supported by procedures that are less costly and logistically challenging than expert consultation. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

White matter correlates of cognitive flexibility in youth with bipolar disorder and typically developing children and adolescents.

Prior studies using behavioral tasks and neuroimaging have shown that children and adolescents with bipolar disorder (BD) have deficits in cognitive flexibility (CF)-defined as adaptation to changing rewards and punishments. However, no study, to our knowledge, has examined the white matter microstructural correlates of CF in youth with BD. To address this gap, we examined the relationship between CF assessed with the Cambridge Neuropsychological Testing Automated Battery (CANTAB)'s Intra-Extra Dimensional Set Shift task (ID/ED) and diffusion tensor imaging analyzed with FSL's preprocessing tools and Tract-Based Spatial Statistics (TBSS). We found a significantly different relationship between microstructural integrity of multiple white matter regions and CF performance in BD (n=28) and age-matched typically developing control (TDC) youths (n=26). Evaluation of the slopes of linear regressions in BD vs. TDC (ID/ED Simple Reversal error rate vs. fractional anisotropy) revealed significantly different slopes across the groups, indicating an aberrant relationship between CF and underlying white matter microstructure in youth with BD. These results underscore the importance of examining specific CF-neuroimaging relationships in BD youth. Future longitudinal studies could seek to define the white matter microstructural trajectories in BD vs. TDC, and relative to CF deficits and BD illness course.

Safety Planning Intervention for Adolescents: Provider Attitudes and Response to Training in the Emergency Services Setting.

OBJECTIVE: This study aimed to describe the implementation of the empirically supported Safety Planning Intervention (SPI) for adolescent suicidality in emergency services (ES) settings. METHODS: Using an implementation science framework, the authors collaboratively evaluated the needs of ES providers; developed a plan; and trained ES psychiatrists, social workers, and mental health specialists for SPI implementation. The health care and social workers put the safety plan into practice in ES settings and, after involving stakeholders in addressing challenges during implementation, fully integrated the program into ES practice. This study examined providers' attitudes toward the structured SPI before and after training in this evidence-based intervention. RESULTS: Providers reported a desire to learn evidence-based interventions for safety planning before the training. The effect of time from pre- to posttraining on provider attitudes and knowledge about the SPI was statistically significant (F=4.19, df=2 and 22, p=0.030), indicating that providers' attitudes toward using the structured SPI in their work improved after completing the training. CONCLUSIONS: These findings are relevant for health care settings that seek to comply with new standards for hospital accreditation and improve overall patient care for suicidal youths. The results suggest that stakeholder collaboration and brief training in SPI may be effective for incorporating structured safety planning practices into pediatric ES settings.

Do styles of emotion dysregulation differentiate adolescents engaging in non-suicidal self-injury from those attempting suicide?

Emotion dysregulation is implicated in both suicide attempts (SA) and non-suicidal self-injury (NSSI). However, little is known about how emotion dysregulation may differ between adolescents who have made an SA from those engaged in NSSI. We sought to address this gap by comparing emotion dysregulation profiles across three homogenous groups of adolescents (1) SA-only (2) NSSI-only (3) and typically developing controls (TDCs). Mean comparisons suggest that adolescents with a history of NSSI reported significantly lower distress tolerance and higher emotional reactivity when compared to adolescents who made an SA. After controlling for shared variance across emotion dysregulation measures, parent report of affective lability was the only scale to uniquely distinguish between NSSI and SA groups. Accurately distinguishing emotion dysregulation patterns across self-injurious groups has practical implications towards assessment, treatment, course of illness, and prevention.

Inflammation-mediated generation and inflammatory potential of human placental cell-free fetal DNA.

INTRODUCTION: Circulating DNA can be pro-inflammatory when detected by leukocytes via toll-like receptor 9 (TLR9). Cell-free fetal DNA (cff-DNA) of placental origin, circulates in pregnancy, and increased concentrations are seen in conditions associated with placental and maternal inflammation such as pre-eclampsia. However, whether cff-DNA is directly pro-inflammatory in pregnant women and what regulates cff-DNA levels in pregnancy are unknown. METHODS: Using a human term placental explant model, we examined whether induction of placental inflammation can promote cff-DNA release, and the capacity of this cff-DNA to stimulate peripheral blood mononuclear cells (PBMCs) from pregnant women. RESULTS: We demonstrate lipopolysaccharide (LPS)-mediated inflammation in placental explants and induced apoptosis after 24 h. However, this did not increase levels of cff-DNA generation compared to controls. Furthermore, the methylation status of the cff-DNA, was not altered by LPS-induced inflammation. Cff-DNA did not elicit production of inflammatory cytokines from PBMCs, in contrast to exposure to LPS or the TLR9 agonist CpG-ODN. Finally, we demonstrate that cff-DNA acquired directly from pregnant women did not differ in methylation status from placental extracted DNA, or from placental explant generated cell-free DNA, and that, unlike Escherichia coli DNA, this cff-DNA has a low level of unmethylated CpG sequences. DISCUSSION: Our data suggest that placental inflammation does not increase release of cff-DNA and that placental cff-DNA is not pro-inflammatory to circulating PBMCs. It thus seems unlikely that high levels of cff-DNA are either a direct consequence or cause of inflammation observed in obstetric complications.

Cervical epithelial damage promotes Ureaplasma parvum ascending infection, intrauterine inflammation and preterm birth induction in mice.

Around 40% of preterm births are attributed to ascending intrauterine infection, and Ureaplasma parvum (UP) is commonly isolated in these cases. Here we present a mouse model of ascending UP infection that resembles human disease, using vaginal inoculation combined with mild cervical injury induced by a common spermicide (Nonoxynol-9, as a surrogate for any mechanism of cervical epithelial damage). We measure bacterial load in a non-invasive manner using a luciferase-expressing UP strain, and post-mortem by qPCR and bacterial titration. Cervical exposure to Nonoxynol-9, 24 h pre-inoculation, facilitates intrauterine UP infection, upregulates pro-inflammatory cytokines, and increases preterm birth rates from 13 to 28%. Our results highlight the crucial role of the cervical epithelium as a barrier against ascending infection. In addition, we expect the mouse model will facilitate further research on the potential links between UP infection and preterm birth.