Faculty Bibliography

Chronic pain is a leading cause of disability, reduced productivity, healthcare seeking behavior, and a contributor to opioid overdose in the United States. For many people, pain can be satisfactorily managed by existing medicines and comprehensive psychosocial treatments. For others, available treatments are either ineffective or not acceptable, due to side effects and concerns about risks. Preliminary evidence suggests that some psychedelics may be effective for certain types of pain and/or improved quality of life with increased functionality and reduced disability and distress in people whose pain may never be completely relieved. Efficacy in these quality-of-life related outcomes would be consistent with the 'reset in thinking' about chronic pain management being increasingly called for as a more realistic goal for some people as compared to complete elimination of pain. This commentary summarizes the rationale for conducting more basic research and clinical trials to further explore the potential for psychedelics in chronic pain management. Additionally, if shown to be effective, to then determine whether the effects of psychedelics are primarily due to direct antinociceptive or anti-inflammatory mechanisms, or via increased tolerability, acceptance, and sense of spirituality, that appear to at least partially mediate the therapeutic effects of psychedelics observed in psychiatric disorders such as major depression. This commentary represents a collaboration of clinical and more basic scientists examining these issues and developing recommendations for research ranging from neuropharmacology to the biopsychosocial treatment factors that appear to be as important in pain management as in depression and other disorders in which psychedelic medicines are under development. This article is part of the Special Issue on "National Institutes of Health Psilocybin Research Speaker Series".

OBJECTIVE:Because changes to pediatric emergency medicine (PEM) education may help address barriers to youth suicide risk screening programs, this study aimed to understand the impact of formal training in areas that likely include suicide-related practices, developmental-behavioral pediatrics (DBP) and adolescent medicine (AM), on PEM physician-perceived level of training, attitudes, and confidence assessing and managing youth suicide risk. METHODS:Twenty-seven PEM attendings and trainees completed an online survey and were divided into 2 groups: those who had completed DBP and AM rotations (DBP/AM+; n = 20) and those who had not completed either rotation (DBP/AM-; n = 7). We compared perceived level of training, attitudes, and confidence in assessing and managing suicide risk across groups. We also examined the relationship between perceived level of training and confidence. Finally, we conducted exploratory analyses to evaluate the effect of an additional formal rotation in child psychiatry. RESULTS:The DBP/AM+ and DBP/AM- groups did not differ on perceived level of training or on attitudes and confidence in suicide risk assessment or management. Perceived level of training in assessment and management predicted confidence in both assessing and managing suicide risk. Additional training in child psychiatry was not associated with increased perceived level of training or confidence. CONCLUSIONS:The DBP and AM rotations were not associated with higher perceived levels of suicide risk training or greater confidence; however, perceived level of training predicted physician confidence, suggesting continued efforts to enhance formal PEM education in mental health would be beneficial.

BACKGROUND:Many patients are currently unable to access psychological treatments for post-traumatic stress disorder (PTSD), and it is unclear which types of therapist-assisted internet-based treatments work best. We aimed to investigate whether a novel internet-delivered cognitive therapy for PTSD (iCT-PTSD), which implements all procedures of a first-line, trauma-focused intervention recommended by the UK National Institute for Health and Care Excellence (NICE) for PTSD, is superior to internet-delivered stress management therapy for PTSD (iStress-PTSD), a comprehensive cognitive behavioural treatment programme focusing on a wide range of coping skills. METHODS:We did a single-blind, randomised controlled trial in three locations in the UK. Participants (≥18 years) were recruited from UK National Health Service (NHS) Improving Access to Psychological Therapies (IAPT) services or by self-referral and met DSM-5 criteria for PTSD to single or multiple events. Participants were randomly allocated by a computer programme (3:3:1) to iCT-PTSD, iStress-PTSD, or a 3-month waiting list with usual NHS care, after which patients who still met PTSD criteria were randomly allocated (1:1) to iCT-PTSD or iStress-PTSD. Randomisation was stratified by location, duration of PTSD (<18 months or ≥18 months), and severity of PTSD symptoms (high vs low). iCT-PTSD and iStress-PTSD were delivered online with therapist support by messages and short weekly phone calls over the first 12 weeks (weekly treatment phase), and three phone calls over the next 3 months (booster phase). The primary outcome was the severity of PTSD symptoms at 13 weeks after random assignment, measured by self-report on the PTSD Checklist for DSM-5 (PCL-5), and analysed by intention-to-treat. Safety was assessed in all participants who started treatment. Process analyses investigated acceptability and compliance with treatment, and candidate moderators and mediators of outcome. The trial was prospectively registered with the ISRCTN registry, ISRCTN16806208. FINDINGS:Of the 217 participants, 158 (73%) self-reported as female, 57 (26%) as male, and two (1%) as other; 170 (78%) were White British, 20 (9%) were other White, six (3%) were Asian, ten (5%) were Black, eight (4%) had a mixed ethnic background, and three (1%) had other ethnic backgrounds. Mean age was 36·36 years (SD 12·11; range 18-71 years). 52 (24%) participants met self-reported criteria for ICD-11 complex PTSD. Fewer than 10% of participants dropped out of each treatment group. iCT-PTSD was superior to iStress-PTSD in reducing PTSD symptoms, showing an adjusted difference on the PCL-5 of -4·92 (95% CI -8·92 to -0·92; p=0·016; standardised effect size d=0·38 [0·07 to 0·69]) for immediate allocations and -5·82 (-9·59 to -2·04; p=0·0027; d=0·44 [0·15 to 0·72]) for all treatment allocations. Both treatments were superior to the waiting list for PCL-5 at 13 weeks (d=1·67 [1·23 to 2·10] for iCT-PTSD and 1·29 [0·85 to 1·72] for iStress-PTSD). The advantages in outcome for iCT-PTSD were greater for participants with high dissociation or complex PTSD symptoms, and mediation analyses showed both treatments worked by changing negative meanings of the trauma, unhelpful coping, and flashback memories. No serious adverse events were reported. INTERPRETATION:Trauma-focused iCT-PTSD is effective and acceptable to patients with PTSD, and superior to a non-trauma-focused cognitive behavioural stress management therapy, suggesting that iCT-PTSD is an effective way of delivering the contents of CT-PTSD, one of the NICE-recommended first-line treatments for PTSD, while reducing therapist time compared with face-to-face therapy. FUNDING:Wellcome Trust, UK National Institute for Health and Care Research Oxford Health Biomedical Research Centre.

OBJECTIVE:The dimensional model of adversity and psychopathology hypothesizes deprivation and threat impact distinct neurobiological pathways, such as brain structure. This hypothesis has not been examined longitudinally or in young children. We tested longitudinal associations between threat and deprivation measured in preschool and brain structure in childhood. We hypothesized threat would be associated with amygdala and hippocampal subcortical volume and deprivation would be associated with cortical thickness in association cortex. METHOD/METHODS:The study included T1-weighted scans from 72 children (5-10 years old, 54.2% female participants). Threat was measured by the presence of domestic violence, sexual abuse, physical abuse, or neighborhood violence. Deprivation was measured by the presence of neglect. We examined associations of deprivation or threat with brain structure controlling for other dimension (deprivation or threat) and nuisance covariates using whole-brain vertex-wise analyses. We extracted subcortical volume and examined the same associations using multiple regression. RESULTS:Threat was associated with widespread decreases in cortical surface area across the prefrontal cortex and other regions. Threat was not associated with amygdala or hippocampal volume. Deprivation was associated with increased thickness in occipital cortex, insula and cingulate. CONCLUSION/CONCLUSIONS:Results suggest distinct associations of deprivation and threat on brain structure in early childhood. Threat is associated with widespread differences in surface area and deprivation is associated with differences in cortical thickness. These observations are consistent with work in adolescence and adulthood and reflect how dimensions of adversity differentially impact neural structure.

There has been considerable speculation regarding the function of the dentate gyrus (DG) - a subregion of the mammalian hippocampus - in learning and memory. In this Perspective article, we compare leading theories of DG function. We note that these theories all critically rely on the generation of distinct patterns of activity in the region to signal differences between experiences and to reduce interference between memories. However, these theories are divided by the roles they attribute to the DG during learning and recall and by the contributions they ascribe to specific inputs or cell types within the DG. These differences influence the information that the DG is thought to impart to downstream structures. We work towards a holistic view of the role of DG in learning and memory by first developing three critical questions to foster a dialogue between the leading theories. We then evaluate the extent to which previous studies address our questions, highlight remaining areas of conflict, and suggest future experiments to bridge these theories.

BACKGROUND:Pragmatic innovations are needed to optimize clinical outcomes among people who use opioids initiating buprenorphine. This pilot randomized controlled trial assessed the feasibility of integrating text messaging in a low threshold telebuprenorphine bridge program for people who use opioids during the COVID-19 pandemic. METHODS:Eligible adult patients with opioid use disorder inducted on buprenorphine (N = 128) in the NYC Health+Hospitals Virtual Buprenorphine Clinic between May and November 2020 were randomized to an automated texting intervention based on the medical management model versus treatment as usual. A participant feedback survey was administered at 8 weeks (n = 18). Primary outcomes consisted of acceptability (eg, study enrollment, engagement with the intervention) and feasibility (eg, lack of phone number and/or mobile phone ownership) of integrating texting in clinical care. A secondary outcome included retention in treatment at week 8 (ie, active buprenorphine prescription within the prior 7 days). RESULTS:Nearly all eligible patients consented to enroll in the study (90.8%) and few were excluded because of lack of mobile phone ownership (n = 27, 14.6%). Requests to discontinue receipt of texts (n = 6, 9.4%) was attributed to excessive message frequency, perceived lack of relevancy, and reduced interest in the intervention. Respondents completing the follow-up feedback survey were generally satisfied with the frequency of software-generated messages (14/18, 77.8%) and half shared text content with peers (9/18, 50%). There were no perceived issues with privacy, intrusiveness, or ease of use. Retention did not differ between participants randomized to the texting (M = 5.23 weeks, SD = 3.41) and treatment as usual groups (M = 4.98 weeks, SD = 3.34) at week 8 ( P = 0.676). CONCLUSIONS:This pilot randomized controlled trial confirms high acceptability and feasibility of integrating an automated texting tool in a telebuprenorphine bridge program. Future studies should assess whether text messaging may be efficacious when combined with staff contact and content addressing social determinants of health.

Infant survival relies on rapid identification, remembering and behavioral responsiveness to caregivers' sensory cues. While neural circuits supporting infant attachment learning have largely remained elusive in children, use of invasive techniques has uncovered some of its features in rodents. During a 10-day sensitive period from birth, newborn rodents associate maternal odors with maternal pleasant or noxious thermo-tactile stimulation, which gives rise to a preference and approach behavior towards these odors, and blockade of avoidance learning. Here we review the neural circuitry supporting this neonatal odor learning, unique compared to adults, focusing specifically on the early roles of neurotransmitters such as glutamate, GABA (Gamma-AminoButyric Acid), serotonin, dopamine and norepinephrine, in the olfactory bulb, the anterior piriform cortex and amygdala. The review highlights the importance of deepening our knowledge of age-specific infant brain neurotransmitters and behavioral functioning that can be translated to improve the well-being of children during typical development and aid in treatment during atypical development in childhood clinical practice, and the care during rearing of domestic animals.

OBJECTIVE/UNASSIGNED:Early-onset behavior disorders (BDs) are common and costly. The evidence-base for Behavioral Parent Training (BPT), the standard of care for early intervention for BDs in young children, is well-established; yet, common comorbidities such as internalizing symptoms are common and their impact, not well understood. The goal of the current study was to examine the potential for technology to improve BPT effects on observed parenting and child behavior outcomes for families of children recruited for clinically significant problem behavior who also presented with relatively higher internalizing symptoms. METHOD/UNASSIGNED: = 101), who are overrepresented in statistics on early-onset BDs, were randomized to an evidence-based BPT program, Helping the Noncompliant Child (HNC), or Technology-Enhanced HNC (TE-HNC). Children were ages 3 to 8 years (55.4% were boys). Child race included White (64.0%), Black or African American (21.0%), more than one race (14.0%), and Hispanic/Latinx (13.9%). RESULTS/UNASSIGNED:Families in both groups evidenced improvement in internalizing symptoms at posttreatment; however, TE-HNC yielded the greatest improvement in positive parenting and child compliance at posttreatment and follow-up for children with the highest internalizing symptoms at baseline. CONCLUSIONS/UNASSIGNED:TE-HNC resulted in improved parenting and child behavior outcomes for children with elevated levels of co-occurring internalizing symptoms at baseline relative to standard HNC. We posit that these added benefits may be a function of TE-HNC, creating the opportunity for therapists to personalize the treatment model boosting parent skill use with more complex presentations, although a formal test of mediation will be important in future work.

AIMS/OBJECTIVE:This study aimed to summarize the evidence on sleep alterations in medication-naïve children and adolescents with autism spectrum disorder (ASD). METHODS:-curve analysis were done. A priori planned meta-regression and subgroup analysis were also performed to identify potential moderators. RESULTS:0.48; 95% CI 0.29 to 0.66). Potential publication bias was detected for sleep latency, sleep period time and total sleep time measured by polysomnography. Some sleep alterations were moderated by age, sex and concurrent intellectual disability. The median NOS score was 8 (interquartile range 7.25-8.75). CONCLUSION/CONCLUSIONS:We found that medication-naïve children and adolescents with ASD presented significantly more subjective and objective sleep alterations compared to TD and identified possible moderators of these differences. Future research requires an analysis of how these sleep alterations are linked to core symptom severity and comorbid behavioural problems, which would provide an integrated therapeutic intervention for ASD. However, our results should be interpreted in light of the potential publication bias.