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BackgroundPavlovian fear paradigms involve learning to associate cues with threat or safety. Aberrances in Pavlovian fear learning correlate with psychopathology, especially anxiety disorders. This study evaluated symptom dimensions of anxiety and depression in relation to Pavlovian fear acquisition and generalization.Methods256 participants (70.31 % female) completed a Pavlovian fear acquisition and generalization paradigm at ages 18-19 and 21-22 years. Analyses focused on indices of learning (self-reported US expectancy, skin conductance). Multilevel models tested associations with orthogonal symptom dimensions (Anhedonia-Apprehension, Fears, General Distress) at each timepoint.ResultsAll dimensions were associated with weaker acquisition of US expectancies at each timepoint. Fears was associated with overgeneralization only at age 21-22. General Distress was associated with overgeneralization only at age 18-19. Anhedonia-Apprehension was associated with overgeneralization at ages 18-19 and 21-22.ConclusionsAnhedonia-Apprehension disrupts Pavlovian fear acquisition and increases overgeneralization of fear. These effects may emerge during adolescence and remain into young adulthood. General Distress and Fears also contribute to overgeneralization of fear, but these effects may vary as prefrontal mechanisms of fear inhibition continue to develop during late adolescence. Targeting specific symptom dimensions, particularly Anhedonia-Apprehension, may decrease fear generalization and augment interventions built on Pavlovian principles, such as exposure therapy.

COVID-19 pandemic-related traumatic stress (PRTS) symptoms are reported in various populations, but risk factors in older adults with chronic medical conditions, remain understudied. We therefore examined correlates and pre-pandemic predictors of PRTS in older adults with hypertension during COVID-19. Participants in California, aged 61-92 years (n = 95), participated in a pre-pandemic healthy aging trial and later completed a COVID-19 assessment (May to September 2020). Those experiencing ⩾1 PRTS symptom (n = 40), and those without PRTS symptoms (n = 55), were compared. The PRTS+ group had poorer mental and general health and greater impairment in instrumental activities of daily living. Pre-pandemic biomarkers of vascular inflammation did not predict increased odds of PRTS; however, greater pre-pandemic anxiety and female gender did predict PRTS during COVID-19. Our findings highlight PRTS as a threat to healthy aging in older adults with hypertension; targeted approaches are needed to mitigate this burden, particularly for females and those with pre-existing anxiety.

Anxiety disorders affect millions of people worldwide and present a challenge in neuroscience research because of their substantial heterogeneity in clinical presentation. While a great deal of progress has been made in understanding the neurobiology of fear and anxiety, these insights have not led to effective treatments. Understanding the relationship between phenotypic heterogeneity and the underlying biology is a critical first step in solving this problem. We show translation, reverse translation, and computational modeling can contribute to a refined, cross-species understanding of fear and anxiety as well as anxiety disorders. More specifically, we outline how animal models can be leveraged to develop testable hypotheses in humans by using targeted, cross-species approaches and ethologically informed behavioral paradigms. We discuss reverse translational approaches that can guide and prioritize animal research in nontraditional research species. Finally, we advocate for the use of computational models to harmonize cross-species and cross-methodology research into anxiety. Together, this translational neuroscience approach will help to bridge the widening gap between how we currently conceptualize and diagnose anxiety disorders, as well as aid in the discovery of better treatments for these conditions.

Short-hairpin RNAs (shRNA), targeting knockdown of specific genes, hold enormous promise for precision-based therapeutics to treat numerous neurodegenerative disorders. However, whether shRNA constructed molecules can modify neuronal circuits underlying certain behaviors has not been explored. We designed shRNA to knockdown the human HTR2A gene in vitro using iPSC-differentiated neurons. Multi-electrode array (MEA) results showed that the knockdown of the 5HT-2A mRNA and receptor protein led to a decrease in spontaneous electrical activity. In vivo, intranasal delivery of AAV9 vectors containing shRNA resulted in a decrease in anxiety-like behavior in mice and a significant improvement in memory in both mice (104%) and rats (92%) compared to vehicle-treated animals. Our demonstration of a non-invasive shRNA delivery platform that can bypass the blood-brain barrier has broad implications for treating numerous neurological mental disorders. Specifically, targeting the HTR2A gene presents a novel therapeutic approach for treating chronic anxiety and age-related cognitive decline.

PurposeTo determine whether a diagnosis of a perinatal mood and anxiety disorder (PMAD) is associated with adverse perinatal outcomes.MethodsMental health symptom screening and diagnostic data from 82 women with single gestation in the Healthy Babies Before Birth study conducted from 2013 to 2018 were obtained by clinic interview. If a woman scored over 10 on the Patient Health Questionnaire (PHQ-9) or endorsed the suicidality item; or scored over 7 on the Overall Anxiety Severity and Impairment Scale (OASIS), a Structured Clinical Interview for DSM-IV (SCID) Axis I Disorders was administered. An adverse perinatal outcome was operationalized as a diagnosis of gestational diabetes mellitus, intrauterine growth restriction, preeclampsia, chorioamnionitis, hemorrhage, fetal death, preterm birth, or a low birthweight baby, and abstracted from the medical records.ResultsWomen were between 22.0 and 45.0 years old (Mean age = 33.1 ± 4.3). Mean BMI was 24.7 ± 5.6 (Range 16.8 to 47.1). Nineteen percent (16) of the 82 women had a SCID diagnosis of a PMAD. Thirty-seven percent (30) had a diagnosed adverse perinatal outcome. Multiple logistic regression was conducted with these predictors: SCID diagnosis of a PMAD, maternal age, BMI. All predictors were significant with respective odds ratios as follows: OR = 3.58, 95% CI 1.03-12.44, p = .045; OR = 2.30, 95% CI 1.21-4.38, p = .011; OR = 1.69, 95% CI 1.06-2.69, p = .027.ConclusionsA PMAD diagnosis was associated with 3.5 times higher odds of having an adverse perinatal outcome. For every 5 years a woman aged or every five units her BMI increased her odds of having an adverse perinatal outcome increased. Older age and increased BMI are well established adverse perinatal outcome risk factors. These results suggest that mental illness risk should also be consistently assessed in obstetric settings.

Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum volumes in PTSD compared to healthy controls (88% trauma-exposed). PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume, as well as reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), vermis (VI, VIII), flocculonodular lobe (lobule X), and corpus medullare (all p-FDR

BACKGROUND: There is currently a deficit of knowledge about how to define, quantify, and measure different aspects of daily routine disruptions amid large-scale disasters like COVID-19, and which psychiatric symptoms were more related to the disruptions. This study aims to conduct a systematic review and meta-analysis on the probable positive associations between daily routine disruptions and mental disorders amid the COVID-19 pandemic and factors that moderated the associations. METHODS: PsycINFO, Web of Science, PubMed, and MEDLINE were systematically searched up to April 2023 (PROSPERO: CRD42023356846). Independent variables included regularity, change in frequency, and change in capability of different daily routines (i.e., physical activity, diet, sleep, social activities, leisure activities, work and studies, home activities, smoking, alcohol, combined multiple routines, unspecified generic routines). Dependent variables included symptoms and/or diagnoses of mental disorders (i.e., depression, anxiety, post-traumatic stress disorder, and general psychological distress). RESULTS: Fifty-three eligible studies (51 independent samples, 910,503 respondents) were conducted in five continents. Daily routine disruptions were positively associated with depressive symptoms (r = 0.13, 95% CI = [0.06; 0.20], p

BACKGROUND: Limited English Proficiency (LEP) Latinxs experience a longer duration of untreated depression and anxiety. LEP Latinxs have difficulty accessing mental healthcare due to insufficient Spanish-speaking behavioral/mental health clinicians to meet demand. These under-resourced healthcare systems are less likely to be the site for the implementation of innovations. Digital interventions can provide an effective option for overcoming these barriers; yet, when digital evidence-based treatments are available, uptake and engagement is often low. This manuscript presents the protocol for the SUPERA (SUpport from PEeRs to expand Access) study which will evaluate the implementation of an evidence-based, Spanish language, digital cognitive-behavioral therapy (dCBT) intervention (i.e., SilverCloud) in safety-net primary care clinics for LEP Latinx patients with depression or anxiety. METHODS: We will conduct an effectiveness-implementation hybrid trial (Type 2) design comparing engagement and clinical outcomes in two modalities of dCBT delivery (peer-supported vs. unsupported). We will also compare provider-level outreach (using a clinic patient registry) versus inreach (traditional provider referral) to compare rates of initiation, completion, and cost. Participants will be 426 LEP Latinx adults ≥18 years of age, PHQ-9 ≥ 10 or GAD-7 ≥ 8, with access to the internet via smartphone, and not currently receiving individual psychotherapy. We will collect baseline, post-intervention (8 weeks), and follow up (3 months) data. CONCLUSION: The long-term goal of this research is to aid in the implementation of digital mental health interventions that can be sustainably implemented in low-resourced settings, while reducing the reliance on professionals, overcoming workforce deficits, and increasing relevance for diverse populations.

BackgroundSocial determinants of health are consistently associated with systemic lupus erythematosus (SLE) outcomes. However, social determinants of health are typically measured with conventional socioeconomic status factors such as income or education. We assessed the association of economic insecurities (ie, food, housing, health care, and financial insecurity) with patient-reported outcomes in a cohort of patients with SLE.MethodsIn this cross-sectional analysis, data were derived from the California Lupus Epidemiology Study based in the San Francisco Bay Area, CA, USA. Participants were recruited between Feb 25, 2015, and Jan 10, 2018, from rheumatology clinics. Inclusion criteria were Bay Area residency; oral fluency in English, Spanish, Cantonese, or Mandarin; 18 years or older; ability to provide informed consent; and a physician confirmed SLE diagnosis. Food, housing, health care, and financial economic insecurities were assessed by validated screening tools. Patient-reported outcomes were obtained using PROMIS, Quality of Life in Neurological Disorders (known as Neuro-QoL) Cognitive Function short form, Patient Health Questionnaire (PHQ)-8, and General Anxiety Disorder (GAD)-7 instruments. Poverty was defined as household income of 125% or less of the federal poverty limit. Lower education was defined as less than college-graduate education. The association of economic insecurities with patient-reported outcomes was assessed by multivariable linear regression models adjusting for demographics, SLE disease characteristics, and comorbidities. We tested for interactions of insecurities with poverty and education.FindingsThe final cohort included 252 participants. Mean age was 49·7 (SD 13·4) years, 228 (90%) of 252 were women and 24 (10%) were men. 80 (32%) individuals self-identified as Asian, 26 (10%) as Black, 101 (40%) as White, eight (3%) as mixed race, and 37 (15%) as other race; 59 (23%) self-identified as Hispanic. 135 (54%) individuals had at least one insecurity. Insecurities were highly prevalent, and more common in those with poverty and lower education. Adjusted multivariate analyses revealed that participants with any insecurity had significantly worse scores across all measured patient-reported outcomes. For physical function, no insecurity had an adjusted mean score of 48·9 (95% CI 47·5-50·3) and any insecurity had 45·7 (44·3-47·0; p=0·0017). For pain interference, no insecurity was 52·0 (50·5-53·5) and any insecurity was 54·4 (53·0-55·8; p=0·031). For fatigue, no insecurity was 50·5 (48·8-52·3) and any insecurity was 54·9 (53·3-56·5; p=0·0005). For sleep disturbance, no insecurity was 49·9 (48·3-51·6) and any insecurity was 52·9 (51·4-54·5; p=0·012). For cognitive function, no insecurity was 49·3 (47·7-50·9) and any insecurity was 45·6 (44·1-47·0; p=0·0011). For PHQ-8, no insecurity was 4·4 (3·6-5·1) and any insecurity was 6·1 (5·4-6·8; p=0·0013). For GAD-7, no insecurity was 3·3 (2·6-4·1) and any insecurity was 5·2 (4·5-5·9; p=0·0008). Individuals with more insecurities had worse patient-reported outcomes. There were no statistically significant interactions between insecurities and poverty or education.InterpretationHaving any economic insecurity was associated with worse outcomes for people with SLE regardless of poverty or education. The findings of this study provide insight into the relationship between economic insecurities and SLE outcomes and underscore the need to assess whether interventions that directly address these insecurities can reduce health disparities in SLE.FundingUS Centers for Disease Control, Rheumatology Research Foundation, and National Institute of Arthritis and Musculoskeletal and Skin Diseases.

BackgroundTraumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are potential risk factors for the development of dementia including Alzheimer's disease (AD) in later life. The findings of studies investigating this question are inconsistent though.ObjectiveTo investigate if these inconsistencies are caused by the existence of subgroups with different vulnerability for AD pathology and if these subgroups are characterized by atypical tau load/atrophy pattern.MethodsThe MRI and PET data of 89 subjects with or without previous TBI and/or PTSD from the DoD ADNI database were used to calculate an age-corrected gray matter tau mismatch metric (ageN-T mismatch-score and matrix) for each subject. This metric provides a measure to what degree regional tau accumulation drives regional gray matter atrophy (matrix) and can be used to calculate a summary score (score) reflecting the severity of AD pathology in an individual.ResultsThe ageN-T mismatch summary score was positively correlated with whole brain beta-amyloid load and general cognitive function but not with PTSD or TBI severity. Hierarchical cluster analysis identified five different spatial patterns of tau-gray matter interactions. These clusters reflected the different stages of the typical AD tau progression pattern. None was exclusively associated with PTSD and/or TBI.ConclusionsThese findings suggest that a) although subsets of patients with PTSD and/or TBI develop AD-pathology, a history of TBI or PTSD alone or both is not associated with a significantly higher risk to develop AD pathology in later life. b) remote TBI or PTSD do not modify the typical AD pathology distribution pattern.

Anxiety disorders affect millions of people worldwide and impair health, happiness, and productivity on a massive scale. Developmental research points to a connection between early-life behavioral inhibition and the eventual development of these disorders. Our group has previously shown that measures of behavioral inhibition in young rhesus monkeys (Macaca mulatta) predict anxiety-like behavior later in life. In recent years, clinical and basic researchers have implicated the central extended amygdala (EAc)-a neuroanatomical concept that includes the central nucleus of the amygdala (Ce) and the bed nucleus of the stria terminalis (BST)-as a key neural substrate for the expression of anxious and inhibited behavior. An improved understanding of how early-life behavioral inhibition relates to an increased lifetime risk of anxiety disorders-and how this relationship is mediated by alterations in the EAc-could lead to improved treatments and preventive strategies. In this study, we explored the relationships between infant behavioral inhibition and peri-adolescent defensive behavior and brain metabolism in 18 female rhesus monkeys. We coupled a mildly threatening behavioral assay with concurrent multimodal neuroimaging, and related those findings to various measures of infant temperament. To score the behavioral assay, we developed and validated UC-Freeze, a semi-automated machine-learning (ML) tool that uses unsupervised clustering to quantify freezing. Consistent with previous work, we found that heightened Ce metabolism predicted elevated defensive behavior (i.e., more freezing) in the presence of an unfamiliar human intruder. Although we found no link between infant-inhibited temperament and peri-adolescent EAc metabolism or defensive behavior, we did identify infant nervous temperament as a significant predictor of peri-adolescent defensive behavior. Our findings suggest a connection between infant nervous temperament and the eventual development of anxiety and depressive disorders. Moreover, our approach highlights the potential for ML tools to augment existing behavioral neuroscience methods.

Sensory over-responsivity (SOR) is a prevalent cross-diagnostic condition that is often associated with anxiety. The biological mechanisms underlying the co-occurrence of SOR and anxiety symptoms are not well understood, despite having important implications for targeted intervention. We therefore investigated the unique associations of SOR and anxiety symptoms with physiological and neural responses to sensory stimulation for youth with anxiety disorders (ANX), autism spectrum disorder (ASD), or typical development (TD). Age/IQ-matched youth aged 8-18 years (22 ANX; 30 ASD; 22 TD) experienced mildly aversive tactile and auditory stimuli during functional magnetic resonance imaging and then during skin conductance response (SCR) and heart rate (HR) measurements. Caregivers reported on participants' SOR and anxiety symptoms. ASD/ANX youth had elevated SOR and anxiety symptoms compared to TD. ASD/ANX youth showed similar, heightened brain responses to sensory stimulation compared to TD youth, but brain responses were more highly related to SOR symptoms in ASD youth and to anxiety symptoms in ANX youth. Across ASD/ANX youth, anxiety symptoms uniquely related to greater SCR whereas SOR uniquely related to greater HR responses to sensory stimulation. Behavioral and neurobiological over-responsivity to sensory stimulation was shared across diagnostic groups. However, findings support SOR and anxiety as distinct symptoms with unique biological mechanisms, and with different relationships to neural over-reactivity dependent on diagnostic group. Results indicate a need for targeted treatment approaches.

COVID-19 increased the prevalence of clinically significant anxiety in the United States. To investigate contributing factors we analyzed anxiety, reported online via monthly Generalized Anxiety Disorders-7 (GAD-7) surveys between April 2020 and May 2022, in association with self-reported worry about the health effects of COVID-19, economic difficulty, personal COVID-19 experience, and subjective social status. 333,292 anxiety surveys from 50,172 participants (82% non-Hispanic white; 73% female; median age 55, IQR 42-66) showed high levels of anxiety, especially early in the pandemic. Anxiety scores showed strong independent associations with worry about the health effects of COVID-19 for oneself or family members (GAD-7 score +3.28 for highest vs. lowest category; 95% confidence interval: 3.24, 3.33; p

BackgroundWater, sanitation, and hygiene (WaSH) insecurity increases the risk of water-related diseases. However, limited research has been conducted on psychosocial distress as it relates to WaSH insecurity, especially among people who inject drugs (PWID). We examined the relationship between WaSH insecurity and related anxiety among PWID living in different housing conditions along the US-Mexico border region.MethodsFrom 2020-2021, a cross-sectional study was conducted among 585 people who injected drugs within the last month in Tijuana (N = 202), San Diego (N = 182), and in both Tijuana and San Diego (N = 201). Participants underwent interviewer-administered surveys related to WaSH access, substance use, and generalized anxiety disorder (GAD-7). Quasi-Poisson regressions were used to assess associations between WaSH insecurity and anxiety in the prior 6-months.ResultsParticipants were 75% male, 42% were unhoused and 91% experienced WaSH insecurity in the prior 6-months. After adjusting for housing status, gender, and age, lack of access to basic drinking water (Adj RR: 1.28; 95% CI: 1.02-1.58), sanitation (Adj RR:1.28; 95% CI: 1.07-1.55), and a daily bath/shower (Adj RR: 1.38; 95% CI: 1.15-1.66) were associated with mild-severe anxiety. The number of WaSH insecurities was independently associated with a 20% increased risk of experiencing anxiety per every additional insecurity experienced (Adj RR: 1.20; CI: 1.12-1.27). We also found a significant interaction between gender and housing status (p = 0.003), indicating that among people experiencing sheltered/unsheltered homelessness, women had a higher risk of mild-severe anxiety compared to men (Adj RR: 1.55; 95% CI: 1.27-1.89). At the same time, among women, those who are unhoused have 37% increased risk of anxiety than those who live in stable housing conditions (Adj RR: 1.37; 95% CI: 1.01-1.89).ConclusionThe lack of specific WaSH services, particularly lack of drinking water, toilets, and daily showers were associated with higher levels of anxiety among PWID in the Tijuana-San Diego border region. Women experiencing homelessness were especially vulnerable. WaSH interventions that provide safe, 24-h access may help to reduce anxiety and health risks associated with WaSH insecurity.

Anxiety disorders are among the most prevalent psychiatric disorders, causing significant suffering and disability. Relative to other psychiatric disorders, anxiety disorders tend to emerge early in life, supporting the importance of developmental mechanisms in their emergence and maintenance. Behavioral inhibition (BI) is a temperament that emerges early in life and, when stable and extreme, is linked to an increased risk for the later development of anxiety disorders and other stress-related psychopathology. Understanding the neural systems and molecular mechanisms underlying this dispositional risk could provide insight into treatment targets for anxiety disorders. Nonhuman primates (NHPs) have an anxiety-related temperament, called anxious temperament (AT), that is remarkably similar to BI in humans, facilitating the design of highly translational models for studying the early risk for stress-related psychopathology. Because of the recent evolutionary divergence between humans and NHPs, many of the anxiety-related brain regions that contribute to psychopathology are highly similar in terms of their structure and function, particularly with respect to the prefrontal cortex. The orbitofrontal cortex plays a critical role in the flexible encoding and regulation of threat responses, in part through connections with subcortical structures like the amygdala. Here, we explore individual differences in the transcriptional profile of cells within the region, using laser capture microdissection and single nuclear sequencing, providing insight into the molecules underlying individual differences in AT-related function of the pOFC, with a particular focus on previously implicated cellular systems, including neurotrophins and glucocorticoid signaling.

PurposeEvaluate for perturbed signaling pathways associated with subgroups of patients with low versus high levels of state anxiety. These pathways were compared to the pathways identified across eight network pharmacology studies of the anxiolytic effect(s) of a variety of compounds.MethodsAdult outpatients had a diagnosis of breast, gastrointestinal, gynecological, or lung cancer; had received chemotherapy within the preceding four weeks; and were scheduled to receive at least two additional cycles of chemotherapy. Latent profile analysis was used to identify subgroups of patients with distinct anxiety profiles based on Spielberger State Anxiety Inventory scores that were obtained six times over two cycles of chemotherapy. Blood samples were processed using RNA sequencing (i.e., RNA-seq sample, n = 244) and microarray (i.e., microarray sample; n = 256) technologies. Pathway perturbations were assessed using pathway impact analysis. Fisher's combined probability method was used to combine test results using a false discovery rate of 0.01.ResultsIn the RNA-seq sample, 62.3% and 37.7% of the patients were in the low- and high-anxiety classes, respectively. In the microarray sample, 61.3% and 38.7% were in the low and high-anxiety classes, respectively. Forty-one perturbed signaling pathways were identified. Eight of these pathways were common to those identified in the network pharmacology studies.ConclusionsFindings increase our knowledge of the molecular mechanisms that underlie anxiety in patients receiving chemotherapy. This study provides initial insights into how anxiety in patients with cancer may share common mechanisms with anxiety in patients with other clinical conditions.

Attention bias confers risk for anxiety development, however, the influence of sociodemographic variables on the relationship between attention bias and anxiety remains unclear. We examined the association between attention bias and anxiety among rural Latinx youth and investigated potential moderators of this relationship. Clinical symptoms, demographic characteristics, and a performance-based measure of attention bias were collected from 66 rural Latinx youth with clinical levels of anxiety (33.3% female; Mage = 11.74; 92.4% Latinx, 7.6% Mixed Latinx). No moderating effects for age or gender were found. Youth below the poverty line displayed an attention bias away from threat in comparison to youth above the poverty line, who displayed an attention bias towards threat. Among youth below the poverty line, this bias away from threat was associated with increased anxiety. Findings highlight the importance of economic adversity in understanding the relationship between attention bias and anxiety.

To assess the public health impact of the COVID-19 pandemic on mental health, investigators from the National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) research program developed the Pandemic-Related Traumatic Stress Scale (PTSS). Based on the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) acute stress disorder symptom criteria, the PTSS is designed for adolescent (13-21 years) and adult self-report and caregiver-report on 3-12-year-olds. To evaluate psychometric properties, we used PTSS data collected between April 2020 and August 2021 from non-pregnant adult caregivers (n = 11,483), pregnant/postpartum individuals (n = 1,656), adolescents (n = 1,795), and caregivers reporting on 3-12-year-olds (n = 2,896). We used Mokken scale analysis to examine unidimensionality and reliability, Pearson correlations to evaluate relationships with other relevant variables, and analyses of variance to identify regional, age, and sex differences. Mokken analysis resulted in a moderately strong, unidimensional scale that retained nine of the original 10 items. We detected small to moderate positive associations with depression, anxiety, and general stress, and negative associations with life satisfaction. Adult caregivers had the highest PTSS scores, followed by adolescents, pregnant/postpartum individuals, and children. Caregivers of younger children, females, and older youth had higher PTSS scores compared to caregivers of older children, males, and younger youth, respectively. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

OBJECTIVE: The goal of this study was to examine whether neural sensitivity to negative peer evaluation conveys risk for depression among youth with a history of anxiety. We hypothesized that brain activation in regions that process affective salience in response to rejection, relative to acceptance, from virtual peers would predict depressive symptoms 1 year later and would be associated with ecological momentary assessment (EMA) reports of peer connectedness. METHOD: Participants were 38 adolescents ages 11-16 (50% female) with a history of anxiety, recruited from a previous clinical trial. The study was a prospective naturalistic follow-up of depressive symptoms assessed 2 years (Wave 2) and 3 years (Wave 3) following treatment. At Wave 2, participants completed the Chatroom Interact Task during neuroimaging and 16 days of EMA. RESULTS: Controlling for depressive and anxiety symptoms at Wave 2, subgenual anterior cingulate (sgACC; β = .39, p = .010) activation to peer rejection (vs. acceptance) predicted depressive symptoms at Wave 3. SgACC activation to rejection (vs. acceptance) was highly negatively correlated with EMA reports of connectedness with peers in daily life (r = - .71, p

ObjectiveThere is a need for a brief affect scale that also encompasses different components of affect relevant for researchers interested in physiological and health outcomes. The Subcomponents of Affect Scale (SAS) meets this need. This 18-item scale has nine positive and nine negative affect items encompassing six subscales (calm, well-being, vigour, depression, anxiety, anger). Previous research using the SAS has demonstrated its predictive validity, but no work has tested its subscale structure or longitudinal validity.DesignData from the Common Cold Project in which individuals (N = 610) completed the SAS over the course of seven days were used.ResultsConfirmatory factor analysis demonstrated the reliability of the subscale structure of the SAS across seven days (positive affect subscale structure: CFIs ≥ 0.98; negative affect subscale structure: CFIs ≥ 0.94 with day 6 CFI = 0.91) and tests of factorial invariance showed the scale is valid to use over time.ConclusionsThese results confirm the psychometric validity of the subscale structure of the SAS and imply that the subscales can be used longitudinally, allowing for its use in health research as well as non-health research that can benefit from its subscale structure and longitudinal capabilities.

Patients with atypical anorexia nervosa (AAN) or anorexia nervosa (AN) with premorbid history of higher weight (PHW; median BMI ≥ 85th %ile) may report greater eating disorder (ED) pathology, anxiety, and depression, than patients with premorbid history of lower weight (PLW; mBMI  .05). Adolescents with PHW (vs. PLW) were more likely to be diagnosed with AAN (67.9 %, p

Premature dropout from posttraumatic stress disorder treatment (PTSD) hinders treatment response. Studies have primarily used quantitative methodology to identify factors that contribute to Veterans' premature dropout, which has yielded mixed results. Qualitative methods provide rich data and generate additional hypotheses about why Veterans discontinue PTSD treatment. This study aimed to understand Veterans' reasons for dropping out of prolonged exposure therapy (PE) and to examine if there are differences in reasons for dropout between three delivery modalities: in-home, in-person (IHIP), office-based telehealth (OBT), or home-based telehealth (HBT). Twenty-two Veterans who dropped out of PE from a parent randomized clinical trial participated in individual qualitative interviews about potential contextual and individual factors related to discontinuation. Team-based coding was used to conduct open and focused coding. Themes were generated that described factors that influenced Veterans' dropout from PE and constant comparison was used to explore differences in reasons between the three modalities. Most Veterans had multiple reasons for dropping out and reasons were similar across delivery modalities with few differences. Practical barriers (e.g., scheduling difficulties), attitudes toward mental health providers and therapy (e.g., stigma), psychological and physical health factors (e.g., perceived worsening of symptoms, pain), and the therapeutic context (e.g., disliking aspects of PE) contributed to Veterans' decisions to drop out from PE. Veterans in OBT reported more types of practical barriers than Veterans in HBT and IHIP. These findings can help generate hypotheses about interventions that may promote engagement and future studies should continue to study how to reduce dropout. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Fear and anxiety play a central role in mammalian life, and there is considerable interest in clarifying their nature, identifying their biological underpinnings, and determining their consequences for health and disease. Here we provide a roundtable discussion on the nature and biological bases of fear- and anxiety-related states, traits, and disorders. The discussants include scientists familiar with a wide variety of populations and a broad spectrum of techniques. The goal of the roundtable was to take stock of the state of the science and provide a roadmap to the next generation of fear and anxiety research. Much of the discussion centered on the key challenges facing the field, the most fruitful avenues for future research, and emerging opportunities for accelerating discovery, with implications for scientists, funders, and other stakeholders. Understanding fear and anxiety is a matter of practical importance. Anxiety disorders are a leading burden on public health and existing treatments are far from curative, underscoring the urgency of developing a deeper understanding of the factors governing threat-related emotions.

In the present study, we examined the construct validity of scores on the Hebrew version of the Adolescent and Adult Time Inventory-Time Attitudes Scale (AATI-TA). The AATI-TA was translated into Hebrew by bilingual speakers, using the back-translation method. Participants included 452 young adults (Mage = 22.47, SDage = 1.98, 51.5% female). Several measures of psychological well-being were used to establish convergent validity, including scales assessing self-esteem, life satisfaction, and optimism, and depressive, anxiety, and somatic symptoms. Internal consistency estimates for AATI-TA scores were high and confirmatory factor analyses supported the six-factor structure. Correlational analyses indicated the expected relationships between time attitudes and measures of psychological well-being, providing convergent validity support for the AATI-TA scores. The findings of this study support the use of the Hebrew version of the AATI-TA in further studies about time attitudes.

IntroductionAlcohol use disorder (AUD) and PTSD have high rates of co-occurrence in U.S. Military Veterans resulting in incrementally worse functional outcomes relative to having either one of these disorders alone. Cognitive dysfunction can impede one's ability to benefit from standard behavioral AUD and PTSD treatments. Cigarette smoking is also highly prevalent among U.S. Military Veterans, and cognitive dysfunction is associated with chronic cigarette use among individuals with AUD and PTSD independently. However, much less is known about to what extent cigarette smoking further impairs cognitive functioning in individuals with both co-occurring AUD and PTSD.Materials and methodsU.S. Veterans with co-occurring AUD and PTSD (n = 162) completed a comprehensive cognitive assessment covering various domains: working memory, processing speed, mental switching, cognitive inhibition, auditory-verbal learning, auditory-verbal memory, and verbal fluency. To examine the impact of alcohol use, traumatic stress, and cigarette smoking on cognitive function, we conducted a three-way interaction examining the moderated effects of smoking status on the association between alcohol use and PTSD symptoms on a composite domain of global cognition.ResultsSmoking status in Veterans with co-occurring AUD and PTSD moderated the relationship between alcohol use and global cognition (P = .042), such that higher levels of alcohol use in the past week were related to worse global cognitive function among Veterans cigarette smokers (P = .015) but not among nonsmokers (P = .833). On follow-up analyses of individual cognitive domains, greater alcohol use in the past week was associated with lower cognitive inhibition in smokers but not nonsmokers, with traumatic stress symptoms moderating this effect (P = .039). Additionally, smoking status moderated the relationship between alcohol use and auditory-verbal learning, such that there was a differential relationship between alcohol use and auditory-verbal learning between smokers and nonsmokers.ConclusionsOverall, results provide evidence for the compounding impact of alcohol use, traumatic stress, and cigarette smoking on cognitive functioning. Impaired cognitive performance on a global level as well as on individual domains of cognitive inhibition and auditory-verbal learning were evident. Cognitive dysfunction may impede a Veteran's ability to benefit from therapeutic treatment, and these cognitive domains may represent potential targets for cognitive training efforts. Further, study results support smoking cessation initiatives and smoke-free policies enacted at Veterans Affairs healthcare facilities and medical centers.

BackgroundPosttraumatic stress disorder (PTSD) is common in primary care patients; however, evidence-based treatments are typically only available in specialty mental healthcare settings and often not accessed.ObjectiveTo test the effectiveness of a brief primary care-based treatment, Clinician-Supported PTSD Coach (CS PTSD Coach) was compared with Primary Care Mental Health Integration-Treatment as Usual (PCMHI-TAU) in (1) reducing PTSD severity, (2) engaging veterans in specialty mental health care, and (3) patient satisfaction with care.DesignMulti-site randomized pragmatic clinical trial.ParticipantsA total of 234 veterans with PTSD symptoms who were not currently accessing PTSD treatment.InterventionCS PTSD Coach was designed to be implemented in Veterans Affairs PCMHI and combines mental health clinician support with the "PTSD Coach" mobile app. Four 30-min sessions encourage daily use of symptom management strategies.Main measuresPTSD severity was measured by clinician-rated interviews pre- and post-treatment (8 weeks). Self-report measures assessed PTSD, depression, and quality of life at pretreatment, posttreatment, and 16- and 24-week follow-ups, and patient satisfaction at post-treatment. Mental healthcare utilization was extracted from medical records.Key resultsClinician-rated PTSD severity did not differ by condition at post-treatment. CS PTSD Coach participants improved more on patient-reported PTSD severity at post-treatment than TAU participants (D = .28, p = .021). Coach participants who continued to have problematic PTSD symptoms at post-treatment were not more likely to engage in 2 sessions of specialty mental health treatment than TAU participants. Coach participants engaged in 74% more sessions in the intervention and reported higher treatment satisfaction than TAU participants (p

The primary objective of this article is to consider the impact of the coronavirus disease-19 pandemic on pediatric anxiety from both a clinical and system-of-care lens. This includes illustrating the impact of the pandemic on pediatric anxiety disorders and consideration of factors important for special populations, including children with disabilities and learning differences. We consider the clinical, educational, and public health implications for addressing mental health needs like anxiety disorders and how we might promote better outcomes, particularly for vulnerable children and youth.

Disparities in treatment engagement and adherence based on ethnicity have been widely recognized but are inadequately understood. Few studies have examined treatment dropout among Latinx and non-Latinx White (NLW) individuals. Using Andersens Behavioral Model of Health Service Use (A behavioral model of families use of health services. 1968; J Health Soc Behav. 1995; 36:1-10) as a framework, we examine whether pretreatment variables (categorized as predisposing, enabling, and need factors) mediate the relationship between ethnicity and premature dropout in a sample of Latinx and NLW primary care patients with anxiety disorders who participated in a randomized controlled trial (RCT) of cognitive behavioral therapy. Data from a total of 353 primary care patients were examined; 96 Latinx and 257 NLW patients participated. Results indicated that Latinx patients dropped out of treatment more often than NLW patients, resulting in roughly 58% of Latinx patients failing to complete treatment compared with 42% of NLW, and approximately 29% of Latinx patients dropping out before engaging in modules related to cognitive restructuring or exposure, relative to 11% of NLW patients. Mediation analyses suggest that social support and somatization partially explained the relationship between ethnicity and treatment dropout, highlighting the importance of these variables in understanding treatment disparities.

OBJECTIVE: A 6-week study was conducted to test the effectiveness of the Harnessing Online Peer Education (HOPE) intervention on anxiety, help seeking (requests for electronic resources [e-resources] on anxiety reduction), and online engagement. METHODS: Three hundred participants with moderate to severe anxiety (i.e., seven-item Generalized Anxiety Disorder scale [GAD-7] scores ≥10) were randomly assigned to social media (i.e., Facebook) groups with or without peer leaders. The study was conducted from April 5 to May 17, 2020. GAD-7 scores, e-resource requests, and online engagement were measured at baseline and at weeks 2, 4, and 6. RESULTS: GAD-7 scores improved in both intervention and control groups, with no difference between conditions. Participants in the intervention group were more likely than those in the control group to request e-resources (OR=10.27, 95% CI=4.52-23.35) and engage online (OR=2.84, 95% CI=1.70-4.76). CONCLUSIONS: The HOPE intervention effectively promoted mental health help-seeking behavior and online engagement.

ObjectiveThis study is a non-randomized pragmatic trial to assess the feasibility and acceptability of the Primary Care Intervention for Posttraumatic stress disorder (PCIP) (Srivastava et al., 2021), an Integrated Behavioral Health Care treatment for PTSD in adolescents.MethodFollowing routine clinic procedures, youth who were suspected of having trauma-related mental health symptoms were referred by their primary care providers to integrated care social workers for evaluation. The integrated care social workers referred the first 23 youth whom they suspected of having PTSD to the research study. Twenty youth consented to the study and 19 completed the pre-assessment (17 female; mean age = 19.32, SD = 2.11; range 14-22 years). More than 40% identified as Black and a third as Hispanic/Latinx. PCIP mechanisms and clinical outcomes were assessed pre- and post-treatment, and at one-month follow-up. Participants and therapists completed post-treatment qualitative interviews to assess feasibility and acceptability, and treatment sessions were audio recorded to assess fidelity.ResultsFindings suggest high acceptability, satisfaction, and feasibility of the PCIP delivered in "real-life" safety net pediatric primary care. Integrated care social workers had high treatment fidelity. Despite the small sample size, there was significant improvement in symptom scores of anxiety (g = 0.68, p = 0.02) and substance use (g = 0.36, p = 0.04) from pre to post, and depression symptoms (g = 0.38, p = 0.04) from pre to follow-up. Qualitative data from patients who completed exit interviews and integrated social workers indicated high satisfaction with the treatment, with some participants reporting that the integrated intervention was more acceptable and less stigmatizing than seeking mental health care outside of primary care.ConclusionsThe PCIP may improve treatment engagement and access for vulnerable youth. Promising findings of high acceptability, feasibility, and initial clinical effectiveness suggest that PCIP warrants larger-scale study as part of routine care in pediatric integrated care.

BackgroundSocial support is associated with decreased symptoms of postpartum mood and anxiety disorders (PMAD) in mothers of healthy infants, but less is known about social support and PMADs in mothers with preterm infants. The purpose of this study was to examine the relationship between social support and symptoms of PMADs reported by mothers in the months following hospital discharge of their preterm infant.MethodsMothers of infants less than 33 weeks gestational age were enrolled from neonatal intensive care units (NICU) at 6 sites. Mothers completed PMAD measures of depression, anxiety and post-traumatic stress approximately 3 months following their infant's discharge. Multivariable regression was used to evaluate relationships between social support and PMAD measures.ResultsOf 129 mothers, 1 in 5 reported clinically significant PMAD symptoms of: depression (24%), anxiety (19%), and post-traumatic stress (20%). Social support was strongly inversely associated with all 3 PMADs. Social support explained between 21% and 26% of the variance in depression, anxiety and post-traumatic stress symptoms.ConclusionIncreased social support may buffer PMAD symptoms in mothers of preterm infants after discharge. Research is needed to determine effective screening and interventions aimed at promoting social support for all parents during and following their infant's hospitalisation.

Youth in the juvenile justice system evince high rates of mental health symptoms, including anxiety and depression. How these symptom profiles change after first contact with the justice system and - importantly - how they are related to re-offending remains unclear. Here, we use latent growth curve modeling to characterize univariate and multivariate growth of anxiety, depression, and re-offending in 1216 male adolescents over 5 years following their first arrest. Overall, the group showed significant linear and quadratic growth in internalizing symptoms and offending behaviors over time such that levels decreased initially after first arrest followed by a small but significant upturn occurring a few years later. Crucially, multivariate growth models revealed strong positive relationships between the rates of growth in internalizing symptoms and offending behaviors such that improvements in mental health related to greater decreases in offending, and vice versa. These results highlight the reciprocal nature of internalizing and externalizing problems in adolescence, underscoring the importance of considering mental health alongside offending in the juvenile justice system.

The neurophysiological mechanisms in the human amygdala that underlie post-traumatic stress disorder (PTSD) remain poorly understood. In a first-of-its-kind pilot study, we recorded intracranial electroencephalographic data longitudinally (over one year) in two male individuals with amygdala electrodes implanted for the management of treatment-resistant PTSD (TR-PTSD) under clinical trial NCT04152993. To determine electrophysiological signatures related to emotionally aversive and clinically relevant states (trial primary endpoint), we characterized neural activity during unpleasant portions of three separate paradigms (negative emotional image viewing, listening to recordings of participant-specific trauma-related memories, and at-home-periods of symptom exacerbation). We found selective increases in amygdala theta (5-9 Hz) bandpower across all three negative experiences. Subsequent use of elevations in low-frequency amygdala bandpower as a trigger for closed-loop neuromodulation led to significant reductions in TR-PTSD symptoms (trial secondary endpoint) following one year of treatment as well as reductions in aversive-related amygdala theta activity. Altogether, our findings provide early evidence that elevated amygdala theta activity across a range of negative-related behavioral states may be a promising target for future closed-loop neuromodulation therapies in PTSD.

Post-traumatic stress disorder (PTSD) is a multisystem syndrome. Integration of systems-level multi-modal datasets can provide a molecular understanding of PTSD. Proteomic, metabolomic, and epigenomic assays are conducted on blood samples of two cohorts of well-characterized PTSD cases and controls: 340 veterans and 180 active-duty soldiers. All participants had been deployed to Iraq and/or Afghanistan and exposed to military-service-related criterion A trauma. Molecular signatures are identified from a discovery cohort of 218 veterans (109/109 PTSD+/-). Identified molecular signatures are tested in 122 separate veterans (62/60 PTSD+/-) and in 180 active-duty soldiers (PTSD+/-). Molecular profiles are computationally integrated with upstream regulators (genetic/methylation/microRNAs) and functional units (mRNAs/proteins/metabolites). Reproducible molecular features of PTSD are identified, including activated inflammation, oxidative stress, metabolic dysregulation, and impaired angiogenesis. These processes may play a role in psychiatric and physical comorbidities, including impaired repair/wound healing mechanisms and cardiovascular, metabolic, and psychiatric diseases.

BackgroundDepression and anxiety-related disorders are common among adolescents. Research attention to early adolescence and low-income ethnically diverse populations is limited.AimTo conduct screening for depression and anxiety at an early age with attention to gender and socioenvironmental context within a low-income setting.MethodMixed methods included the PHQ-9A and GAD-10 screening instruments and ethnographic interviews.Results75 ethnically diverse middle school students were included. Mean years age was 11.2 (0.74). Females had higher PHQ-9A sum scores than males (p = .002, Mann-Whitney test) and higher GAD-10 sum scores than males (p = .016, Mann-Whitney test). After controlling for multiple comparisons, girls had higher mean responses on three PHQ-9A items (p

BackgroundDysfunction in major stress response systems during the acute aftermath of trauma may contribute to risk for developing posttraumatic stress disorder (PTSD). The current study investigated how PTSD diagnosis and symptom severity, depressive symptoms, and childhood trauma uniquely relate to diurnal neuroendocrine secretion (cortisol and alpha-amylase rhythms) in women who recently experienced interpersonal trauma compared to non-traumatized controls (NTCs).MethodUsing a longitudinal design, we examined diurnal cortisol and alpha-amylase rhythms in 98 young women (n = 57 exposed to recent interpersonal trauma, n = 41 NTCs). Participants provided saliva samples and completed symptom measures at baseline and 1-, 3-, and 6-month follow-up.ResultsMultilevel models (MLMs) revealed lower waking cortisol predicted the development of PTSD in trauma survivors and distinguished at-risk women from NTCs. Women with greater childhood trauma exposure exhibited flatter diurnal cortisol slopes. Among trauma-exposed individuals, lower waking cortisol levels were associated with higher concurrent PTSD symptom severity. Regarding alpha-amylase, MLMs revealed women with greater childhood trauma exposure exhibited higher waking alpha-amylase and slower diurnal alpha-amylase increase.ConclusionsResults suggest lower waking cortisol in the acute aftermath of trauma may be implicated in PTSD onset and maintenance. Findings also suggest childhood trauma may predict a different pattern of dysfunction in stress response systems following subsequent trauma exposure than the stress system dynamics associated with PTSD risk; childhood trauma appears to be associated with flattened diurnal cortisol and alpha-amylase slopes, as well as higher waking alpha-amylase.

STUDY OBJECTIVES: To assess the association of insomnia symptoms and psychiatric symptoms in patients with spinal cord injury or disease (SCI/D). METHODS: In this cross-sectional observational study, veterans with SCI/D (n = 72; mean = 59.85 ± 10.4 years; 92% male) completed baseline measures, including the Insomnia Severity Index (ISI) during the baseline phase of a clinical trial on treatment of sleep disorders in veterans with SCI/D. Depression severity was measured by the Patient Health Questionnaire (PHQ-9; sleep items excluded), anxiety severity was measured by the Generalized Anxiety Disorder screener (GAD-7), and probable posttraumatic stress disorder (PTSD) was measured by the Primary Care PTSD screener. Blocked regression was used to evaluate the impact of insomnia symptoms (ISI) on mental health measures after accounting for demographics and level of spinal cord injury/disease. RESULTS: On average, participants scored in the mild range for depression (PHQ-9 = 7.4 ± 5.9) and anxiety severity (GAD-7 = 6.1 ± 6.1). In total, 36.1% (n = 26) screened positive for probable PTSD. ISI explained 19% of the variance in PHQ-9 and 20% of the variance in GAD-7 (P < .001) over and above demographics and SCI/D level of injury/disease. Odds of probable PTSD were increased 1.22-fold for each 1 unit increase in ISI (P = .001) after accounting for demographics and level of injury/disease. CONCLUSIONS: In veterans with SCI/D, insomnia severity was linked to depression and anxiety symptom severity and risk of PTSD. Study results warrant further research to evaluate the impact of insomnia treatment on depression, anxiety, and PTSD in patients with SCI/D. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Treatment of Sleep-disordered Breathing in Patients With SCI; URL: https://clinicaltrials.gov/ct2/show/NCT02830074; Identifier: NCT02830074. CITATION: Kelly MR, Zeineddine S, Mitchell MN, et al. Insomnia severity predicts depression, anxiety, and posttraumatic stress disorder in veterans with spinal cord injury or disease: a cross-sectional observational study. J Clin Sleep Med. 2023;19(4):695-701.

OBJECTIVE: Cognitive-behavioral therapy (CBT) is considered a first-line treatment for obsessive-compulsive disorder (OCD) in pediatric and adult populations. Nevertheless, some patients show partial or null response. The identification of predictors of CBT response may improve clinical management of patients with OCD. Here, we aimed to identify structural magnetic resonance imaging (MRI) predictors of CBT response in 2 large series of children and adults with OCD from the worldwide ENIGMA-OCD consortium. METHOD: Data from 16 datasets from 13 international sites were included in the study. We assessed which variations in baseline cortical thickness, cortical surface area, and subcortical volume predicted response to CBT (percentage of baseline to post-treatment symptom reduction) in 2 samples totaling 168 children and adolescents (age range 5-17.5 years) and 318 adult patients (age range 18-63 years) with OCD. Mixed linear models with random intercept were used to account for potential cross-site differences in imaging values. RESULTS: Significant results were observed exclusively in the pediatric sample. Right prefrontal cortex thickness was positively associated with the percentage of CBT response. In a post hoc analysis, we observed that the specific changes accounting for this relationship were a higher thickness of the frontal pole and the rostral middle frontal gyrus. We observed no significant effects of age, sex, or medication on our findings. CONCLUSION: Higher cortical thickness in specific right prefrontal cortex regions may be important for CBT response in children with OCD. Our findings suggest that the right prefrontal cortex plays a relevant role in the mechanisms of action of CBT in children.

Women's social experiences can have long-term implications for their offspring's health, but little is known about the potential independent contributions of multiple periods of stress exposures over time. This study examined associations of maternal exposure to adversity in childhood and pregnancy with children's anxiety and depression symptoms in a large, sociodemographically diverse sample. Participants were 1389 mother-child dyads (child age M = 8.83 years; SD = 0.66; 42% Black, 42% White; 6% Hispanic) in the ECHO-PATHWAYS Consortium's three U.S. pregnancy cohorts. Women reported their exposure to childhood traumatic events (CTE) and pregnancy stressful life events (PSLE). Children self-reported on their symptoms of anxiety and depression at age 8-9 years. Regression analyses estimated associations between maternal stressors and children's internalizing problems, adjusting for confounders, and examined child sex as a modifier. Exploratory interaction analyses examined whether geospatially-linked postnatal neighborhood quality buffered effects. In adjusted models, PSLE counts positively predicted levels of children's anxiety and depression symptoms ([ßAnxiety=0.08, 95%CI [0.02, 0.13]; ßDepression=0.09, 95%CI [0.03, 0.14]); no significant associations were observed with CTE. Each additional PSLE increased odds of clinically significant anxiety symptoms by 9% (95%CI [0.02, 0.17]). Neither sex nor neighborhood quality moderated relations. Maternal stressors during pregnancy appear to have associations with middle childhood anxiety and depression across diverse sociodemographic contexts, whereas maternal history of childhood adversity may not. Effects appear comparable for boys and girls. Policies and programs addressing prevention of childhood internalizing symptoms may benefit from considering prenatal origins and the potential two-generation impact of pregnancy stress prevention and intervention.

This multi-method study examined perspectives on mindfulness and coping strategies used by trauma-exposed women experiencing homelessness (WEH), residing in a state-funded residential drug treatment site in Southern California (United States). Questionnaires and in-depth focus group interviews were utilised to examine traumatic experiences over the lifespan, probable-posttraumatic stress disorder (PTSD), and coping strategies. Mindfulness was explored as a potential way to improve coping; potential benefits and challenges associated with implementing a mindfulness-based intervention (MBI) with trauma-exposed WEH were also investigated. A Community Advisory Board (CAB) was formed to identify key issues experienced by WEH and to develop a semi structured interview guide (SSIG). Using the SSIG, women participated in one of four focus groups (total N = 28; n = 7 per group). Quantitative data on demographic indicators, probable-PTSD, and trauma exposure were collected. Almost 90% of women met criteria for probable-PTSD; trauma exposure was exceedingly high; most women had experienced multiple traumas throughout their lives. Four main themes emerged from qualitative analyses, which drew from Grounded Theory and used open, selective, and axial coding: (1) ways of coping with trauma; (2) perspectives on mindfulness; (3) prior experiences with mindfulness; and (4) challenges for conducting a mindfulness programme. Overall, WEH used a variety of coping techniques to deal with their trauma, had some familiarity with mindfulness, and were optimistic an MBI would be helpful, despite identifying several challenges to implementation. MBIs may be helpful adjuncts to traditional care for trauma-exposed, WEH, recovering from substance use disorder. Population-specific considerations may improve implementation and participation.

INTRODUCTION: There are unmet mental health needs of depressed adolescents and young adults (AYAs) across the USA. Behavioural technology adequately integrated into clinical care delivery has potential to improve care access and efficiency. This multisite randomised controlled trial evaluates how a coach-enhanced digital cognitive behavioural intervention (dCBI) enhances usual care for depressed AYAs in paediatric practices with minority enriched samples. METHODS AND ANALYSIS: Participants (n=750) ages 16-22 who meet threshold criteria for depressive severity (Patient Health Questionnaire-9; PHQ-9 score 10-24) will be recruited through paediatric practices across three academic institutions (Boston, Pittsburgh and San Diego). Participants will be randomised to 12 weeks of dCBI+treatment as usual (TAU) (n=450) or TAU alone (n=300) in outpatient paediatric practices. Assessments will be completed at baseline, 6 weeks and 12 weeks with the primary outcome being improvement in clinician-rated and self-reported depressive severity (Childrens Depression Rating Scale-Revised and PHQ-9) and secondary outcomes being self-reported suicidal ideation (item 9 on PHQ-9), anxiety severity (Generalised Anxiety Disorder), general quality of life (Satisfaction with Life Scale) and general functioning (Childrens Global Assessment Scale). The study design is an intent-to-treat mixed effects regression with group, and covariates nested within the sites. ETHICS AND DISSEMINATION: All participants or their parent/guardian (under 18 years or unemancipated) will give informed consent to a study team member. All data are expected to be collected over 18 months. The Institutional Review Board (IRB) is a board at each institution in the United States that reviews and monitors research involving human subjects. IRB approval from the University of Pittsburgh was obtained on 30 November 2021 (STUDY21080150), from the University of California San Diegos Human Research Protection Program IRB on 14 July 2022 (802047), and from the Boston Childrens Hospital IRB on 25 October 2022 (P00040987). Full study results are planned to be published within 2 years of initial study recruitment (October 2024). Dissemination of findings will occur in peer-reviewed journals, professional conferences and through reports to participating entities and stakeholders. TRIAL REGISTRATION NUMBER: NCT05159713; ClinicalTrials.gov.

IntroductionThe Impact Stratification Score (ISS) is a measure of the impact of chronic low back pain (LBP) consisting of nine Patient-Reported Outcomes Measurement Information System (PROMIS-29) items, but no studies have examined the ISS or its association with psychological symptoms in military samples. This study examines longitudinal associations between psychological symptoms and the ISS among military service members.Material and methodsThe study involved secondary data analysis of a sample of active duty U.S. military service members aged 18-50 years with LBP (n = 733). Participants completed the PROMIS-29 at three time points during treatment: baseline (time 1, T1), week 6 of treatment (time 2, T2), and week 12 of treatment (time 3, T3). The impact of LBP was quantified using the ISS (ranging from 8 = least impact to 50 = greatest impact). Psychological symptoms were assessed as PROMIS-29 anxiety and depression scores. Separate autoregressive cross-lagged models examined reciprocal associations of ISSs with anxiety, depression, and emotional distress scores from T1 to T3.ResultsWithin each time point, the ISS was significantly and positively correlated with anxiety and depression. In autoregressive cross-lagged models, anxiety and depression predicted the ISS at the next time point and associations were similar in magnitude (e.g., anxiety T2 to ISS T3: β = 0.12, P

BACKGROUND AND OBJECTIVES: Mood, anxiety disorders, and suicidality are more frequent in people with epilepsy than in the general population. Yet, their prevalence and the types of mood and anxiety disorders associated with suicidality at the time of the epilepsy diagnosis are not established. We sought to answer these questions in patients with newly diagnosed focal epilepsy and to assess their association with suicidal ideation and attempts. METHODS: The data were derived from the Human Epilepsy Project study. A total of 347 consecutive adults aged 18-60 years with newly diagnosed focal epilepsy were enrolled within 4 months of starting treatment. The types of mood and anxiety disorders were identified with the Mini International Neuropsychiatric Interview, whereas suicidal ideation (lifetime, current, active, and passive) and suicidal attempts (lifetime and current) were established with the Columbia Suicidality Severity Rating Scale (CSSRS). Statistical analyses included the t test, χ2 statistics, and logistic regression analyses. RESULTS: A total of 151 (43.5%) patients had a psychiatric diagnosis; 134 (38.6%) met the criteria for a mood and/or anxiety disorder, and 75 (21.6%) reported suicidal ideation with or without attempts. Mood (23.6%) and anxiety (27.4%) disorders had comparable prevalence rates, whereas both disorders occurred together in 43 patients (12.4%). Major depressive disorders (MDDs) had a slightly higher prevalence than bipolar disorders (BPDs) (9.5% vs 6.9%, respectively). Explanatory variables of suicidality included MDD, BPD, panic disorders, and agoraphobia, with BPD and panic disorders being the strongest variables, particularly for active suicidal ideation and suicidal attempts. DISCUSSION: In patients with newly diagnosed focal epilepsy, the prevalence of mood, anxiety disorders, and suicidality is higher than in the general population and comparable to those of patients with established epilepsy. Their recognition at the time of the initial epilepsy evaluation is of the essence.

OBJECTIVE: No widely accepted clinical guidelines, and scant directly applicable pragmatic research, are available to guide the prescription of psychiatric medications in low-threshold outpatient settings, such as street outreach, urgent care, and crisis care, as well as walk-in, shelter, and bridge and transition clinics. Providers frequently prescribe medications in these settings without patients having firm psychiatric diagnoses and without medical records to guide clinical decision making. Persons who receive medications in these settings often seek help voluntarily and intermittently for mental illness symptoms. However, because of structural and individual factors, such patients may not engage in longitudinal outpatient psychiatric care. The authors reviewed the literature on psychiatric medication prescribing in low-threshold settings and offer clinical considerations for such prescribing. METHODS: The authors conducted a rapid literature review (N=2,215 abstracts), which was augmented with up-to-date clinical prescribing literature, the authors collective clinical experience, and DSM-5 section II diagnostic criteria to provide considerations for prescribing medications in low-threshold settings. RESULTS: For individuals for whom diagnostic uncertainty is prominent, a symptom-based diagnostic and treatment approach may be best suited to weigh the risks and benefits of medication use in low-threshold settings. Practical considerations for treating patients with clinical presentations of psychosis and trauma, as well as mood, anxiety, and substance use disorders, in low-threshold settings are discussed. CONCLUSIONS: An urgent need exists to invest in pragmatic research and guideline development to delineate best-practice prescribing in low-threshold settings.

We examined the associations between time perspective and mental health outcomes (N = 337; Mage = 22.74, SDage = 5.59; 76% female). Time perspective included multiple dimensions (feelings, frequency, orientation, and relation) and time periods (past, present, and future). Mental health outcomes included depressive symptoms, anxiety, and rumination. To demonstrate the reliability of the time perspective scales, test-retest analyses were completed. Multivariate analyses showed that (a) positive feelings about time were associated with lower anxiety; (b) negative feelings about time were associated with greater anxiety; and (c) more frequent thoughts about the past were associated with greater depressive symptoms and anxiety. Associations remained when controlling for anxiety and depressive symptoms, respectively. Moreover, (a) positive feelings about time were associated with lower rumination; (b) negative feelings about time were associated with greater rumination; and (c) more frequent thoughts about the past were associated with greater rumination. Time perspective scales yielded scores that were moderate to high in test-retest reliability. Findings demonstrate the value of examining separate time perspective dimensions and time periods. Results highlight the role of time perspective in mental health interventions for adults.

AimComorbid anxiety disorder is related to greater illness severity among individuals at clinical high risk (CHR) for psychosis, but its potential role in moderating response to Family Focused Therapy (FFT) for CHR is unexamined. We investigated whether comorbid anxiety disorder in CHR individuals is associated with less constructive communication during family problem-solving interactions, whether their communication skills differentially improve after FFT, and whether FFT is effective in reducing anxiety in this population.MethodsIndividuals recruited into the second phase of the 8-site North American Prodrome Longitudinal Study (NAPLS2) participated (N = 129). They were randomly assigned to 18-sessions of FFT-CHR or three-sessions of Enhanced Care (EC). Participants completed a diagnostic interview at pre-treatment, a family interaction task at pre-treatment and 6-months, and a self-report anxiety measure at pretreatment, 6 and 12-months.ResultsIndividuals at CHR with comorbid anxiety engaged in more negative and fewer positive behaviours during family problem-solving interactions at pre-treatment than did those without comorbid anxiety. There was a significant interaction between anxiety diagnosis and time on interactional behaviour scores, such that individuals at CHR with an anxiety diagnosis showed a greater decrease in negative behaviours and increase in positive behaviours from baseline to 6-months than those without anxiety disorder(s) regardless of treatment condition. However, individuals' self-reported anxiety symptoms decreased more in FFT-CHR than in EC from pre-treatment to 12-month follow-up, regardless of anxiety diagnoses.ConclusionsIndividuals at CHR with symptoms of anxiety benefit from family interventions in showing reductions in anxiety and improvements in family communication.

BackgroundInterest in complementary and integrative health (CIH) approaches, such as meditation, yoga, and acupuncture, continues to grow. The evidence of effectiveness for some CIH approaches has increased in the last decade, especially for pain, with many being recommended in varying degrees in national guidelines. To offer nonpharmacological health management options and meet patient demand, the nation's largest integrated healthcare system, the Veterans Health Administration (VA), greatly expanded their provision of CIH approaches recently.ObjectiveThis paper addressed the questions of how many VA patients might use CIH approaches and chiropractic care if they were available at modest to no fee, and would patients with some health conditions or characteristics be more likely than others to use these therapies.DesignUsing electronic medical records, we conducted a national, three-year, retrospective analysis of VA patients' use of eleven VA-covered therapies: chiropractic care, acupuncture, Battlefield Acupuncture, biofeedback, clinical hypnosis, guided imagery, massage therapy, meditation, Tai Chi/Qigong, and yoga.ParticipantsWe created a national cohort of veterans using VA healthcare from October 2016-September 2019.Key resultsVeterans' use of these approaches increased 70% in three years. By 2019, use was 5.7% among all VA patients, but highest among patients with chronic musculoskeletal pain (13.9%), post-traumatic stress disorder (PTSD; 10.6%), depression (10.4%), anxiety (10.2%), or obesity (7.8%). The approach used varied by age and race/ethnicity, with women being uniformly more likely than men to use each approach. Patients having chronic musculoskeletal pain, obesity, anxiety, depression, or PTSD were more likely than others to use each of the approaches.ConclusionsVeterans' use of some approaches rapidly grew recently and was robust, especially among patients most in need. This information might help shape federal/state health policy on the provision of evidence-based CIH approaches and guide other healthcare institutions considering providing them.

Trauma-informed beliefs often decrease during posttraumatic stress disorder (PTSD) treatment. This may also extend to anxiety sensitivity (AS), defined as a fear of anxiety-related sensations and beliefs that anxiety is dangerous and/or intolerable. However, little is known about how AS changes during exposure-based and psychopharmacological PTSD treatments. Further, high AS may be a risk factor for diminished PTSD symptom improvement and increased treatment dropout. To better understand how AS impacts and is impacted by PTSD treatment, we conducted a secondary analysis of a randomized clinical trial with a sample of 223 veterans (87.0% male, 57.5% White) with PTSD from four U.S. sites. Veterans were randomized to receive prolonged exposure (PE) plus placebo (n = 74), sertraline plus enhanced medication management (n = 74), or PE plus sertraline (n = 75). Veterans answered questions about PTSD symptoms and AS at baseline and 6-, 12-, 24-, 36-, and 52-week follow-ups. High baseline AS was related to high levels of PTSD severity at 24 weeks across all conditions, β = .244, p = .013, but did not predict dropout from exposure-based, β = .077, p = .374, or psychopharmacological therapy, β = .009, p = .893. AS also significantly decreased across all three treatment arms, with no between-group differences; these reductions were maintained at the 52-week follow-up. These findings suggest that high AS is a risk factor for attenuated PTSD treatment response but also provide evidence that AS can be improved by both PE and an enhanced psychopharmacological intervention for PTSD.

BackgroundBetween 20 % and 30 % of teens suffer from depression or anxiety before reaching adulthood, and up to half also use or misuse alcohol. Although theories suggest bidirectional links between harmful alcohol use (e.g., binge drinking) and internalizing symptoms (i.e., depression and anxiety), empirical evidence to-date has been mixed. Systematic reviews have attributed mixed findings to limitations in study design, such as the utilization of between-person analyses and the focus on unidirectional effects. The goal of this study was to address these limitations by assessing bidirectional within-person associations between internalizing symptoms and binge drinking over the course of 5 years in the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) sample, a large cohort recruited at ages 12-21 and followed annually on substance use and psychiatric functioning.MethodsWe used latent curve models with structured residuals to examine within-person lagged associations between depression, anxiety, and past month counts of binge drinking using NCANDA data (N = 831). Analyses were supplemented with post-hoc power simulations.ResultsWe found marginal evidence linking binge drinking with subsequent depression symptoms one year later among females. We found no evidence that depression or anxiety predicted subsequent binge drinking despite sufficient power.ConclusionsSocial and cognitive consequences of binge drinking may predict later depression symptoms in adolescence and young adulthood for young women, though there was little evidence favoring self-medication models for binge drinking. We note several moderating variables and common factor mechanisms that may better explain this link.

Oxytocin (OT) is involved in the regulation of physiological processes and emotional states, with increasing evidence for its beneficial actions being mediated by the autonomic and immune systems. Growing evidence suggests that OT plays a role in the pathophysiology of different psychiatric disorders. Given the limited information in humans the aim of this study was to retrospectively explore plasma OT levels in psychiatric patients, particularly focusing on sex-related differences, as compared with healthy controls. The patients studied here were divided into three groups diagnosed with obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD) or major depressive disorder (MDD). Plasma OT levels were significantly different between healthy men and women, with the latter showing higher values, while none of the three psychiatric groups showed sex-related differences in the parameters measured here. The intergroup analyses showed that the OT levels were significantly higher in OCD, lower in PTSD and even more reduced in MDD patients than in healthy subjects. These differences were also confirmed when gender was considered, with the exception of PTSD men, in whom OT levels were similar to those of healthy men. The present results indicated that OT levels were higher amongst healthy women than men, while a sex difference was less apparent or reversed in psychiatric patients. Reductions in sex differences in psychopathologies may be related to differential vulnerabilities in processes associated with basic adaptive and social functions.