Faculty Bibliography

The placenta adapts to maternal environment and its alterations may have a lasting impact on child's temperament development. Prenatal stress has been linked to both a downregulation of monoamine oxidase A (MAOA) gene expression in the placenta and to difficult temperament. Capitalizing on an ongoing longitudinal study, we analysed data from 95 mother-child dyads to investigate whether MAOA mediates the association between prenatal stress and infant temperament. Prenatal stress was defined as exposure to Superstorm Sandy (Sandy) during pregnancy. Infant temperament was measured by Infant Behaviour Questionnaire-Revised. MAOA gene expression was quantified in placenta tissue. The Smiling and Laughter subscale score was independently associated with Sandy exposure and MAOA placental gene expression. Mediation analysis confirmed that MAOA expression partially mediated the relationship between Sandy and Smiling and Laughter subscale, suggesting that in utero exposure to Sandy could induce lower frequency of smiling and laughter via downregulation of placental MAOA gene expression. These effects could compromise optimal temperamental trajectory and contribute to risk for psychological problems. Placental epigenetic markers can contribute to a multidimensional model of early intervention for high-risk children.

Limited research has examined the relation between exposure to stressors and internalizing symptoms among Latino adolescents, including factors that account for this relation. This study examined whether sleep played a role in the relation between exposure to neighborhood- (i.e., neighborhood disadvantage) and individual-level (i.e., negative life events) stressors and symptoms of anxiety and depression among a sample of 144 low-income, Latino adolescents (54% males, mean age = 16.25, SD = 1.46) attending a charter high school in a large, Midwestern city. The bias corrected bootstrap method was used to evaluate indirect effects. Significant findings indicated an indirect effect via sleep problems in the link between negative life events and anxiety. Alternative models were also explored. Results suggest that sleep problems are important to consider for interventions among Latino youth, particularly those exposed to neighborhood and individual stressors, as this may also have implications for reducing internalizing symptoms among this population. (PsycINFO Database Record

After a hiatus of some 40 years, clinical research has resumed on the use of classic hallucinogens to treat addiction. Following completion of a small open-label feasibility study, we are currently conducting a double-blind placebo-controlled clinical trial of psilocybin-assisted treatment of alcohol use disorder. Although treatment effects cannot be analyzed until the study is complete, descriptive case studies provide a useful window into the therapeutic process of psychedelic-assisted treatment of addiction. Here we describe treatment trajectories of three participants in the ongoing trial to illustrate the range of experiences and persisting effects of psilocybin treatment. Although it is difficult to generalize from a few cases, several qualitative conclusions can be drawn from the data presented here. Although participants often find it difficult to describe much of their psilocybin experience, pivotal moments tend to be individualized, extremely vivid, and memorable. Often, the qualitative content extends beyond the clinical problem that is being addressed. The participants discussed in this paper experienced acute and lasting alterations in their perceptions of self, in the quality of their baseline consciousness, and in their relationship with alcohol and drinking. In these cases, experiences of catharsis, forgiveness, self-compassion, and love were at least as salient as classic mystical content. Finally, feelings of increased "spaciousness" or mindfulness, and increased control over choices and behavior were reported following the drug administration sessions. Ultimately, psilocybin-assisted treatment appears to elicit experiences that are extremely variable, yet seem to meet the particular needs of the individual.

Human and animal models suggest that maternal hormonal and physiological adaptations during pregnancy shape maternal brain functioning and behavior crucial for offspring care and survival. Less sensitive maternal behavior, often associated with psychobiological dysregulation and the offspring's behavioral and emotional disorders, has been observed in mothers who have experienced adverse childhood experiences. Strong evidence shows that children who are exposed to domestic violence (DV) are at risk of being abused or becoming abusive in adulthood. Yet little is known about the effect of childhood exposure to DV on the expecting mother, her subsequent caregiving behavior and related effects on her infant. Thus, the present study examined the association of maternal exposure to DV during childhood on prenatal maternal attachment, maternal heart rate reactivity to an infant-crying stimulus and post-natal infant emotional regulation. Thirty-three women with and without exposure to DV during childhood were recruited during the first trimester of pregnancy and followed until 6-month after birth. The Maternal Antenatal Attachment Scale (MAAS) was used to measure prenatal attachment of the mother to her fetus during the second trimester of pregnancy, maternal and fetal heart rate reactivity to an infant-crying stimulus was assessed at the third trimester of pregnancy, and the Infant Behavior Questionnaire-Revised (IBQ-R) was used to assess infant emotional regulation at 6-months. Results showed that pregnant women that were exposed to DV during childhood had a poorer quality of prenatal attachment of mother to fetus, regardless of whether they also experienced DV during adulthood. In addition, maternal exposure to DV during childhood was associated with increased maternal heart rate to infant-crying stimulus and worse infant emotional regulation. These findings highlight the importance of prenatal screening for maternal exposure to DV during childhood as a risk factor for disturbances in the development of maternal attachment, dysfunctional maternal behavior and emotion dysregulation.

Background/UNASSIGNED:Neurofibromatosis 1 (NF1) is a monogenic model for syndromic autism. Statins rescue the social and cognitive phenotype in animal knockout models, but translational trials with subjects > 8 years using cognition/behaviour outcomes have shown mixed results. This trial breaks new ground by studying statin effects for the first time in younger children with NF1 and co-morbid autism and by using multiparametric imaging outcomes. Methods/UNASSIGNED:A single-site triple-blind RCT of simvastatin vs. placebo was done. Assessment (baseline and 12-week endpoint) included peripheral MAPK assay, awake magnetic resonance imaging spectroscopy (MRS; GABA and glutamate+glutamine (Glx)), arterial spin labelling (ASL), apparent diffusion coefficient (ADC), resting state functional MRI, and autism behavioural outcomes (Aberrant Behaviour Checklist and Clinical Global Impression). Results/UNASSIGNED: = 0.25) at baseline. Three of 12 (25%) simvastatin cases compared to none in placebo met 'clinical responder' criteria for behavioural outcome. Conclusions/UNASSIGNED:We show feasibility of peripheral MAPK assay and autism symptom measurement, but the study was not powered to test effectiveness. Multiparametric imaging suggests possible simvastatin effects in brain areas previously associated with NF1 pathophysiology and the social brain network. Trial registration/UNASSIGNED:EU Clinical Trial Register (EudraCT) 2012-005742-38 (www.clinicaltrialsregister.eu).

A developing brain shows intense reorganization and heightened neuronal plasticity allowing for environmental modulation of its development. During early life, maternal care is a key factor of this environment and defects in this care can derail adaptive brain development and may result in susceptibility to neuropsychiatric disorders. Nevertheless, the mechanisms by which those maternal interactions immediately impact the offspring's brain activity to initiate the pathway to pathology are not well understood. We do know that multiple neurotransmitter systems are involved, including the serotonergic system, a key neuromodulator involved in brain development and emotional regulation. We tested the importance of the serotonergic system and pups' immediate neural response to maternal presence using wireless electrophysiological recordings, a novel approach allowing us to record neural activity during pups' interactions with their mother. We found that maternal contact modulates the P10-P12 rat pups' anterior cingulate cortex (ACC) activity by notably increasing local-field potential (LFP) power in low-frequency bands. We demonstrated, by blocking serotonergic receptors, that this increase is mediated through 5-HT2 receptors (5-HT2Rs). Finally, we showed in isolated pups that enhancing serotonergic transmission, using a selective-serotonin-reuptake-inhibitor, is sufficient to enhance LFP power in low-frequency bands in a pattern similar to that observed when the mother is in the nest. Our results highlight a significant contribution of the serotonergic system in mediating changes of cortical activity in pups related to maternal presence.