Faculty Bibliography

Anxiety disorders are the most prevalent mental health conditions worldwide. While their burden in terms of excess mortality is known to be high, a quantitative systematic evaluation of all-cause and cause-specific mortality and suicide attempt risks in people with anxiety or stress-related disorders is lacking. We performed a systematic review and random effects meta-analysis, in which co-primary outcomes were risk ratios (RRs) for all-cause and suicide-related mortality, and secondary outcomes were natural-cause mortality, other cause-specific mortality, and risk of suicide attempt. Sensitivity and meta-regression analyses were conducted. Overall, 165 studies encompassing 7,395,722 people with any anxiety or stress-related disorder and 135,059,023 controls, from 27 different countries across all continents, were included. Compared with the general population, a higher risk of all-cause mortality was associated with any anxiety or stress-related disorder (n=42, RR=1.54, 95% CI: 1.14-2.08, p=0.005), generalized anxiety disorder (n=9, RR=1.48, 95% CI: 1.23-1.78, p<0.001), and post-traumatic stress disorder (PTSD) and other stress-related disorders (n=21, RR=1.39, 95% CI: 1.15-1.67, p<0.001), but not with panic disorder, phobias, and mixed anxiety or stress-related disorders. Suicide mortality was increased in people with any anxiety or stress-related disorder (n=39, RR=2.88, 95% CI: 2.13-3.89, p<0.001), panic disorder (n=3, RR=3.58, 95% CI: 1.39-9.25, p<0.008), mixed anxiety or stress-related disorders (n=27, RR=2.77, 95% CI: 1.89-4.07, p<0.001), PTSD and other stress-related disorders (n=11, RR=3.13, 95% CI: 1.85-5.28, p<0.001), and generalized anxiety disorder (n=3, RR=1.93, 95% CI: 1.17-3.17, p<0.01). Suicide attempt risk was higher than in the general population in people with all anxiety or stress-related disorders, ranging from RR=6.33 (95% CI: 4.08-9.82, n=5) in panic disorder to RR=2.74 (95% CI: 1.72-4.35, n=5) in phobias. Natural-cause mortality was increased in any anxiety or stress-related disorder (n=19, RR=1.25, 95% CI: 1.09-1.44, p=0.002), generalized anxiety disorder (n=5, RR=1.55, 95% CI: 1.19-2.02, p=0.001), mixed anxiety or stress-related disorders (n=8, RR=1.26, 95% CI: 1.02-1.56, p=0.033), and PTSD and other stress-related disorders (n=9, RR=1.17, 95% CI: 1.03-1.33, p=0.019), but not in panic disorder. Cardiovascular-related deaths were increased in any and mixed anxiety or stress-related disorders and in generalized anxiety disorder, while cancer mortality was increased only in generalized anxiety disorder. When analyzing people with vs. without anxiety disorders with samples being matched by comorbid physical or mental disorders, results remained significant for all-cause mortality in generalized anxiety disorder and panic disorder, but not in any or mixed anxiety or stress-related disorders, and in PTSD and stress-related disorders. When compared with other mental disorders, no difference in co-primary outcomes emerged from more than two studies. Publication bias was present across several analyses, but sensitivity analyses largely confirmed the main findings. In meta-regression analyses, more recent data collection mitigated all-cause mortality, while schizophrenia-spectrum and bipolar disorder comorbidity mitigated suicide mortality risk, possibly driven by underlying treatment. This meta-analysis documents a higher all-cause, suicide and natural-cause mortality, and a higher risk of suicide attempt, in people with anxiety or stress-related disorders compared to the general population. Given the high prevalence and the recognized global treatment gap for these disorders, this finding is of great public health concern, and calls for appropriate prevention, screening and treatment strategies. More studies are needed to fill the publication bias gap and to identify modifiable risk or mitigating factors.

It is estimated that, globally, the mean point prevalence of diagnosable mental disorders in children and adolescents is higher than 11%, and around half of cases of major mental disorders have their onset before the age of 18. Mental disorders with onset in childhood or adolescence have an enormous impact on the developing brain, body and personal identity, as well as on the short- and long-term social, educational and functional capacity of individuals. Child and adolescent psychiatry - as a discipline, profession, academic field, and network of clinical services - is still relatively young, with its formal evolution beginning in the 20th century. Therefore, it is not surprising that there are currently many challenges, but also opportunities and expected future developments, in this area. In this paper, we identify and address the core challenges, possible solutions, opportunities, and future directions of child and adolescent psychiatry. In the first part of the paper, challenges and possible solutions are discussed regarding diagnostic issues, stigma, access to care, shortage of mental health professionals, evidence-based treatments, treatment adherence, parental participation/engagement, integration with schools, digital influences and cyberbullying, and war/forced displacement. In the second part, opportunities and developments are addressed that relate to early identification and intervention, resilience, interdisciplinary collaborations, integration with primary care, community-based approaches, use of digital technologies, precision child and adolescent psychiatry, artificial intelligence and related ethical issues, and cultural diversity and competences. Despite the significance and impact of mental disorders in children and adolescents, clinical delivery and research on these conditions remain underfunded and underprioritized, even in high-income countries, with clinical services and prevention/early intervention research receiving minimal investment. Addressing mental health in children and young people requires multi-level strategies beyond individual treatment, including tackling structural and socioeconomic barriers and creating opportunities for strengthening resilience and well-being. A well-trained workforce, adequate policies, and increased public awareness are crucial. Overall, the current gaps demand urgent action and global funding rebalancing to more adequately meet the critical needs of children and young people challenged by mental illness.

Autistic youth visit the emergency department (ED) for psychiatric concerns, including suicidal ideation and behavior, at elevated rates. However, clinicians often report low levels of training and confidence in addressing suicide risk in autistic youth. In this pilot study, clinicians in a pediatric psychiatric emergency service were trained on community- and evidence-informed recommendations to improve suicide-related care for autistic youth and provided with resources to use with autistic youth for a 3-month period. Ratings on attitudes and confidence were obtained from ten providers before and after the training/implementation period and compared. Ratings of feasibility and utility of strategies and resources were obtained from 15 providers after training/implementation and analyzed. While no changes were found across attitudes items, confidence scores were significantly higher after the training/implementation period than before, particularly in the area of suicide risk assessment. Feasibility and utility ratings were generally high, with endorsement patterns aligning with common organizational and systems-level barriers. This pilot study demonstrated that targeted training and evidence-informed recommendations to improve suicide-related care for autistic youth were associated with increased clinician confidence. As research continues in the development of adapted suicide risk assessment tools and management strategies for autistic youth, it is important that both clinical guidance on best practices is provided and that systems-level barriers are addressed.

INTRODUCTION/UNASSIGNED:This article features the application of Causal Data Science (CDS) methods to determine the mechanism for Posttraumatic Stress (PTS) in young, maltreated children, in order to advance knowledge for prevention. Advances in prevention require research that identifies causal factors, but the scientific literature that would inform the identification of causes are almost exclusively based on the application of correlational methods to observational data. Causal inferences from such research will frequently be in error. We conducted the present study to explore the application of CDS methods as an alternative-or a supplement-to experimental methods, which can rarely be applied in human research on causal factors for PTS. METHODS/UNASSIGNED:A data processing pipeline that integrates state-of-the-art CDS algorithms was applied to an existing observational, longitudinal data set collected by the Consortium for Longitudinal Studies in Child Abuse and Neglect (LONGSCAN). This data set contains a sample of 1,354 children who were identified in infancy to early childhood as being maltreated or at risk. RESULTS/UNASSIGNED:A causal network model of 251 variables (nodes) and 818 bivariate relations (edges) was discovered, revealing four direct causes (Emotional Maltreatment at age 0-4, Physical Assault at age 8, Feeling of Safety at age 8, and Witnessing Violence at age 8) and two direct effects (Negative Self-Image and Severe Assault from a Non-Caregiver at age 8) of PTS at age 8, within a network containing a broad diversity of causal pathways. DISCUSSION/UNASSIGNED:These results indicate that CDS methods show promise for research on the complex etiology of PTS in young, maltreated children.

INTRODUCTION/UNASSIGNED:Autism spectrum disorder (ASD) is characterized in part by differences in pragmatic (i.e., social) language use. However, few studies on pragmatic language have included a meaningful number of autistic females, and even fewer have evaluated pragmatic language profiles for sex-specific differences. The existing literature on pragmatic language in autistic individuals without intellectual disability suggests that females may have stronger social communication skills compared to males, but findings are mixed, and there is not a clear profile of specific pragmatic skills that are liable to sex differences. It is also important to develop novel methodologies, such as computational methods, to characterize pragmatic language in ways less labor-intensive than gold-standard hand-coding methods, which are extremely time consuming and typically not feasible in clinical settings. METHODS/UNASSIGNED:The present study examined hand coding of pragmatic language data samples alongside multiple computational linguistic methodological approaches to characterize sex differences in pragmatic language in autistic males and females across narrative and semi-structured conversational tasks that might reveal context-specific patterns across sex and diagnostic groups. RESULTS/UNASSIGNED:Results indicated that most pragmatic domains differed between autistic and non-autistic groups, with autistic males showing the most obvious pragmatic differences, and that differences between diagnostic groups were more pronounced in the semi-structured conversational context. The alignment between computational and hand-coded findings was strongest in domains with clear theoretical overlap (e.g., frequency of emotional words) but was less consistent in areas that were less theoretically aligned (e.g., conversational dynamics and single word function). DISCUSSION/UNASSIGNED:These findings support the promise of computational methods for characterizing narrative abilities, though further study including validation against hand-coded approaches is warranted.

BACKGROUND:Autism spectrum disorder (ASD) has a complex inheritance pattern and is more common in males. Etiological models suggest that majority of ASD risk is transmitted through common and rare de-novo genetic variation. It has been hypothesized that rare variation could be inherited and therefore contribute to the overall risk-burden in subsequent generations, especially through female lineage in disorders with male-skewed sex-ratios. Here we test this hypothesis using multigeneration information on paternal age, because burden of de-novo mutations has been linked to paternal age, and there is a well-established association between older age of fathers and ASD. METHODS:We analyzed combined data from Sweden's, Denmark's and Finland's national registers totaling 12.6 million family-members, including information about parental ages at the time of birth of offspring in two generations, and ASD diagnosis in the third generation. RESULTS:Among the 1,808,892 children in the third generation, 23,397 (1.29%) were diagnosed with ASD. Increased paternal age at the time of birth of a daughter was associated with increased risk of ASD in the daughter's own offspring. Increased paternal age at the time of birth of a son was not associated with increased ASD risk in the son's offspring, nor was older maternal age in the first or second generations. We observed that young maternal age at birth of a son or a daughter was associated with ASD risk in their offspring. CONCLUSIONS:Collectively, our results suggest that etiologic risk-factors for ASD could extend over multiple generations through different underlying mechanisms, suggesting new directions for research on genetic and non-genetic risk-factors.

INTRODUCTION/UNASSIGNED:Poor dental health is linked to poor physical and mental health. This study was aimed to examine the characteristics of U.S. adults that are associated with having seen a dentist in the past year. METHODS/UNASSIGNED:A cross-section of adults aged 18-64 years (N=19,975) from the 2023 National Health Interview Survey was examined. Bivariate analyses examined the associations of sociodemographic and financial variables with recent dental visits in the last 12 months. Multinomial modeling was used to assess these variables to predict 3 outcomes of time since the last dental visit: in the last 12 months; over a year but <10 years; and over 10 years or never, which was the reference category. RESULTS/UNASSIGNED:In young and middle-aged adults, 4.8% of Americans, representing over 9 million people, had either never seen a dentist or not seen a dentist in 10 years or more. The likelihood of a dental visit in the last 12 months increased with education level (no high-school degree versus a graduate or professional degree [AOR=0.21, 95% CI=0.09, 0.50]) and income (income below the federal poverty line versus income in the highest quartile [AOR=0.20, 95% CI=0.11, 0.35]). Having dental coverage in a private plan or Medicaid, compared with having no coverage, predicted having a dental visit within the last 12 months in both multinomial and bivariate analyses. CONCLUSIONS/UNASSIGNED:Access to dental care in young and middle-aged adults is determined by financial ability. Increasing access to dental care could happen once the financial barriers to dental care are reduced, including increasing the age at which a young adult can be covered by a parent's plan and making dental coverage comparable with physical health coverage. Given the current data about the links between dental, mental, and physical health, parity for all care is warranted.

The collection of electroencephalography (EEG) data in neonates typically occurs during sleep. EEG activity is highly sleep-state dependent, therefore differentiating between states during data processing can provide important insights into neurodevelopment. Despite this, there have been a paucity of studies directly comparing how infant EEG data, especially event-related potentials, differ between these sleep states. Here, we adapted the Maryland Analysis of Developmental EEG pipeline (MADE) to integrate sleep-state coding into its automated preprocessing pipeline. We recorded EEG in 102 sleeping one month old infants and evaluated their responses during a resting state and during a three-stimuli auditory oddball paradigm. Examination of resting-state power revealed significant differences between two sleep states, namely active (AS) and quiet (QS) sleep across all frequency bands in both absolute and relative power. For the auditory oddball paradigm, we computed responses to both standard and deviant tones and then created a difference score reflecting the Mismatch Response (MMR). For the novel tones we examined the evoked response (P300). Results revealed for the MMR, a significant electrode cluster by sleep-state interaction (F = 5.36, p = .01), indicating that the MMR was present at all three electrode clusters during AS (p-values <.05), but only at the frontal cluster during QS (t = 2.05, p = .04). There were no differences in the amplitude of the P300 to the novel sound as a function of sleep state.