Faculty Bibliography

Recent randomized controlled trials of psilocybin-assisted psychotherapy for patients with cancer suggest that this treatment results in large-magnitude reductions in anxiety and depression as well as improvements in attitudes toward disease progression and death, quality of life, and spirituality. To better understand these findings, we sought to identify psychological mechanisms of action using qualitative methods to study patient experiences in psilocybin-assisted psychotherapy. Semistructured interviews were conducted with 13 adult participants with clinically elevated anxiety associated with a cancer diagnosis who received a single dose of psilocybin under close clinical supervision. Transcribed interviews were analyzed using interpretative phenomenological analysis, which resulted in 10 themes, focused specifically on cancer, death and dying, and healing narratives. Participants spoke to the anxiety and trauma related to cancer, and perceived lack of available emotional support. Participants described the immersive and distressing effects of the psilocybin session, which led to reconciliations with death, an acknowledgment of cancer's place in life, and emotional uncoupling from cancer. Participants made spiritual or religious interpretations of their experience, and the psilocybin therapy helped facilitate a felt reconnection to life, a reclaiming of presence, and greater confidence in the face of cancer recurrence. Implications for theory and clinical treatment are discussed.

Youth with psychiatric and behavioral complaints commonly present to emergency departments (EDs), which often lack dedicated mental health staff. This article addresses techniques EDs can use to better care for children in need of psychiatric assessment and medical clearance, specifically addressing the evaluation of youth with suicidal ideation and coexisting medical and psychiatric needs. The evaluation and management of youth with agitation and aggression are also discussed. The article concludes with a discussion of systems changes needed to truly improve emergency care for psychiatrically ill youth.

Latent class models are widely used to identify unobserved subgroups (i.e., latent classes) based upon one or more manifest variables. The probability of belonging to each subgroup is typically modeled as a function of a set of measured covariates. In this paper, we extend existing latent class models to incorporate matrix covariates. This research is motivated by a randomized placebo-controlled depression clinical trial. One study goal is to identify a subgroup of subjects who experience symptoms improvement early on during antidepressant treatment, which is considered to be an indication of a placebo rather than a true pharmacological response. We want to relate the likelihood of belonging to this subgroup of early responders to baseline electroencephalography (EEG) measurement that takes the form of a matrix. The proposed method is built upon a low rank Candecomp/Parafac (CP) decomposition of the target coefficient matrix through low-dimensional latent variables, which effectively reduces the model dimensionality. We adopt a Bayesian hierarchical modeling approach to estimate the latent variables, which allows a flexible way to incorporate prior knowledge about covariate effect heterogeneity and offers a data-driven method of regularization. Simulation studies suggest that the proposed method is robust against potentially misspecified rank in the CP decomposition. With the motivating example we show how the proposed method can be applied to extract valuable information from baseline EEG measurements that explains the likelihood of belonging to the early responder subgroup, helping to identify placebo responders and suggesting new targets for the study of placebo response.

The immediate and long-term effects of exposure to early life stress (ELS) have been documented in humans and animal models. Even relatively brief periods of stress during the first 10 days of life in rodents can impact later behavioral regulation and the vulnerability to develop adult pathologies, in particular an impairment of cognitive functions and neurogenesis, but also modified social, emotional, and conditioned fear responses. The development of preclinical models of ELS exposure allows the examination of mechanisms and testing of therapeutic approaches that are not possible in humans. Here, we describe limited bedding and nesting (LBN) procedures, with models that produce altered maternal behavior ranging from fragmentation of care to maltreatment of infants. The purpose of this paper is to discuss important issues related to the implementation of this chronic ELS procedure and to describe some of the most prominent endpoints and consequences, focusing on areas of convergence between laboratories. Effects on the hypothalamic-pituitary adrenal (HPA) axis, gut axis and metabolism are presented in addition to changes in cognitive and emotional functions. Interestingly, recent data have suggested a strong sex difference in some of the reported consequences of the LBN paradigm, with females being more resilient in general than males. As both the chronic and intermittent variants of the LBN procedure have profound consequences on the offspring with minimal external intervention from the investigator, this model is advantageous ecologically and has a large translational potential. In addition to the direct effect of ELS on neurodevelopmental outcomes, exposure to adverse early environments can also have intergenerational impacts on mental health and function in subsequent generation offspring. Thus, advancing our understanding of the effect of ELS on brain and behavioral development is of critical concern for the health and wellbeing of both the current population, and for generations to come.

INTRODUCTION AND AIMS:There is limited research regarding the effects of alcohol consumption by breastfeeding mothers on infant development. This study examined the frequency, correlates and outcomes of alcohol use during lactation. DESIGN AND METHODS:Data were from an Australian cohort study. Maternal demographics and substance use were assessed during pregnancy and at 8 weeks and 12 months postpartum. Breastfeeding duration, infant feeding, sleeping and development (Ages and Stages Questionnaire) were also assessed postpartum. Logistic regression and general linear model analyses examined characteristics of women who drank during breastfeeding, and the association between alcohol use during breastfeeding and infant outcomes. RESULTS:Alcohol use was reported by 60.7% and 69.6% of breastfeeding women at 8 weeks and 12 months postpartum, respectively. Breastfeeding women who consumed alcohol were more likely to be born in Australia or another English-speaking country, be tertiary educated and have higher household incomes. Most drank at low levels (≤14 standard drinks per week, <3 per occasion) and employed strategies (e.g. timing of alcohol use) to minimise alcohol passed onto infants via breastmilk. Alcohol consumption was unrelated to breastfeeding duration, infant feeding and sleeping behaviour at 8 weeks, and most infant developmental outcomes at 8 weeks or 12 months, after adjusting for confounders. The only significant association showed that infants whose mothers drank at 8 weeks postpartum had more favourable results for personal-social development at 12 months compared with those whose mothers abstained. DISCUSSION AND CONCLUSIONS:Low level drinking during breastfeeding is not linked with shorter breastfeeding duration or adverse outcomes in infants up to 12 months of age. [Wilson J, Tay RY, McCormack C, Allsop S, Najman J, Burns L, Olsson CA, Elliott E, Jacobs S, Mattick RP, Hutchinson D. Alcohol consumption by breastfeeding mothers: Frequency, correlates and infant outcomes. Drug Alcohol Rev 2017;00:000-000].

Gender inequalities shape the experience of food insecurity among women living with HIV (WLHIV). We systematically reviewed the impact of food insecurity on sexual risk behaviors and antiretroviral therapy (ART) adherence among WLHIV. We included qualitative or quantitative peer-reviewed articles, extracted data in duplicate, and assessed rigor. Seven studies, from sub-Saharan Africa, North America, and Europe, met inclusion criteria. Food insecurity was associated with increased sexual risk through transactional sex and inability to negotiate safer sex. Hunger and food insecurity were barriers to ART initiation/adherence. Multidimensional programming and policies should simultaneously address poverty, gender inequality, food insecurity, and HIV.

Caregiver report is the most common measure of change in pediatric psychiatry. Yet, placebo response rates pose significant challenges to reliably detect a treatment response. The present study simulated an eight-week clinical trial protocol for Autism Spectrum Disorder (ASD) for the purpose of testing the feasibility and validity of several outcome measures. Twenty caregivers answered questions about their child's behavior on their smartphone each week and completed a battery of paper questionnaires during weeks one and eight. No treatment was administered. Caregivers reported a significant decrease in problem behaviors on the Aberrant Behavior Checklist (ABC) (29% decrease) and general ASD behaviors on the Social Responsiveness Scale (SRS) (7% decrease). There was also a trend of behavior improvement from smartphone questions but no significant changes in clinical ratings of core diagnostic features of ASD. Participation in a comprehensive protocol in the absence of a particular treatment significantly influenced how caregivers perceived the severity of their children's problem behaviors. These placebo-like effects represent substantial challenges for randomized controlled trials (RCTs) that use treatment as usual and have implications for future behavioral and pharmacological treatment trial designs. Autism Res 2017, 10: 1567-1572. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

The dentate gyrus (DG) principal cells are glutamatergic granule cells (GCs), and they are located in a compact cell layer. However, GCs are also present in the adjacent hilar region, but have been described in only a few studies. Therefore, we used the transcription factor prospero homeobox 1 (Prox1) to quantify GCs at postnatal day (PND) 16, 30, and 60 in a common mouse strain, C57BL/6J mice. At PND16, there was a large population of Prox1-immunoreactive (ir) hilar cells, with more in the septal than temporal hippocampus. At PND30 and 60, the size of the hilar Prox1-ir cell population was reduced. Similar numbers of hilar Prox1-expressing cells were observed in PND30 and 60 Swiss Webster mice. Prox1 is usually considered to be a marker of postmitotic GCs. However, many Prox1-ir hilar cells, especially at PND16, were not double-labeled with NeuN, a marker typically found in mature neurons. Most hilar Prox1-positive cells at PND16 co-expressed doublecortin (DCX) and calretinin, markers of immature GCs. Double-labeling with a marker of actively dividing cells, Ki67, was not detected. These results suggest that, surprisingly, a large population of cells in the hilus at PND16 are immature GCs (Type 2b and Type 3 cells). We also asked whether hilar Prox1-ir cell numbers are modifiable. To examine this issue, we conditionally deleted the proapoptotic gene BAX in Nestin-expressing cells at a time when there are numerous immature GCs in the hilus, PND2-8. When these mice were examined at PND60, the numbers of Prox1-ir hilar cells were significantly increased compared to control mice. However, deletion of BAX did not appear to change the proportion that co-expressed NeuN, suggesting that the size of the hilar Prox1-expressing population is modifiable. However, deleting BAX, a major developmental disruption, does not appear to change the proportion that ultimately becomes neurons.