Faculty Bibliography

An interview with Joseph LeDoux, who studies brain mechanisms of emotion, memory, and consciousness.

INTRODUCTION/UNASSIGNED:A large number of randomized controlled trials (RCTs) and observational studies on the pharmacotherapy of ADHD are available. AREAS COVERED/UNASSIGNED:Based on a search in PubMed and PsycInfo (up to 15 September 2022), this review addresses to which extent this body of research is currently able to inform routine prescribing practice, in terms of the choice of medication, titration strategy, augmentation treatments, and use of alternative, non-approved treatments. EXPERT OPINION/UNASSIGNED:A growing body of evidence is informing prescribers on some, but certainly not all, aspects related to the pharmacological treatment of ADHD in the daily clinical practice, with important weaknesses/gaps that need to be addressed. First, evidence synthesis of RCTs is not able to inform decision-making at the individual patient level. Second, the maximum safe and effective doses, possibly beyond those currently recommended, are not well understood. Third, evidence from RCTs on augmenting strategies is still limited. Fourth, no novel agents with the same or higher effect size of stimulants, in terms of efficacy, but with better tolerability and lower abuse potential, have been found. Implementation of precision psychiatry approaches and stratification of patients in future RCTs will be key to, respectively, individualize the treatment strategies and test etiopathophysiology-based agents.

BACKGROUND:Mental and physical health conditions are frequently comorbid. Despite the widespread physiological and behavioral changes during pregnancy, the pattern of comorbidities among women in pregnancy is not well studied. This study aimed to systematically examine the associations between mental and somatic disorders before and during pregnancy. METHOD:The study used data from mothers of a nationally representative birth cohort of children born in Israel (1997-2008). We compared the risk of all major somatic disorders (International Classification of Diseases, Ninth Revision) in pregnant women with and without a mental disorder. All analyses were adjusted for maternal age, child's birth year, family socioeconomic status, and the total number of maternal encounters with health services around pregnancy period. RESULTS:The analytical sample included 77,030 mother-child dyads, with 30,083 unique mothers. The mean age at child's birth was 29.8 years. Prevalence of diagnosis of mental disorder around pregnancy in our sample was 4.4%. Comorbidity between mental and somatic disorders was two times higher than the comorbidity between pairs of different somatic disorders. Of the 17 somatic disorder categories, seven were positively associated with mental health disorders. The highly prevalent comorbidities associated with mental disorders in pregnancy included e.g. musculoskeletal (OR = 1.30; 95% CI = 1.20-1.42) and digestive system diseases (OR = 1.23; 95% CI = 1.13-1.34). CONCLUSIONS:We observed that associations between maternal diagnoses and mental health stand out from the general pattern of comorbidity between nonmental health diseases. The study results confirm the need for screening for mental disorders during pregnancy and for potential comorbid conditions associated with mental disorders.

OBJECTIVE:To investigate cross-sectional and longitudinal associations between parent factors and self-management for youth with spina bifida (SB). METHODS:Participants were 89 camper-parent dyads recruited for a summer camp program for youth with SB (Myouthage = 12.2 years); 48 of these families participated across 2 years. Campers and parents completed assessments at Time 1 (pre-camp) and Time 3 (post-camp) for one or two summers. Parents reported on demographics, their own adjustment, perceptions, attitudes, and behaviors, and youth condition-related responsibility and task mastery. Youth also reported on condition-related responsibility. Hierarchical multiple regression analyses and multilevel modeling were used to examine relationships between parent factors and youth self-management. RESULTS:Parents' expectations for future goal attainment were positively associated with camper responsibility and task mastery, and these associations were moderated by camper age (only significant for older campers). When examining changes over one summer, parental expectations for the future were significantly associated with changes in campers' condition-related task mastery. When examining trajectories across summers, parental perception of child vulnerability was negatively associated with the slope of condition-related responsibility and parents' expectations for future goal attainment were positively associated with the slope of task mastery. CONCLUSIONS:Parent perceptions and behaviors may be important targets for assessment and intervention when promoting condition-related independence for youth with SB.

BACKGROUND:Electroconvulsive therapy (ECT) is an effective and safe medical procedure that mainly indicated for depression, but is also indicated for patients with other conditions. However, ECT is among the most stigmatized and controversial treatments in medicine. Our objective was to examine social media contents on Twitter related to ECT to identify and evaluate public views on the matter. METHODS:We collected Twitter posts in English and Spanish mentioning ECT between January 1, 2019 and October 31, 2020. Identified tweets were subject to a mixed method quantitative-qualitative content and sentiment analysis combining manual and semi-supervised natural language processing machine-learning analyses. Such analyses identified the distribution of tweets, their public interest (retweets and likes per tweet), and sentiment for the observed different categories of Twitter users and contents. RESULTS:"Healthcare providers" users produced more tweets (25%) than "people with lived experience" and their "relatives" (including family members and close friends or acquaintances) (10% combined), and were the main publishers of "medical" content (mostly related to ECT's main indications). However, more than half of the total tweets had "joke or trivializing" contents, and such had a higher like and retweet ratio. Among those tweets manifesting personal opinions on ECT, around 75% of them had a negative sentiment. CONCLUSIONS:Mixed method analysis of social media contents on Twitter offers a novel perspective to examine public opinion on ECT, and our results show attitudes more negative than those reflected in studies using surveys and other traditional methods.

The classical psychedelic psilocybin is of interest as a treatment for alcohol use disorder (AUD). This study investigated the effects of psilocybin on voluntary ethanol consumption in adult male and female C57BL/6J mice administered saline or psilocybin intraperitoneally as a single dose of 0.1, 0.5, 1.0 or 2.0 mg/kg and provided 20% ethanol utilizing a two-bottle choice alcohol drinking paradigm. Ethanol was provided continuously for 3 days immediately following the administration of psilocybin, then withheld for 2 days, and then provided continuously for two subsequent additional days. A multilevel model (MLM) for repeated measures was used to compare ethanol consumption and preference in psilocybin-treated groups versus controls. Ethanol consumption and preference were reduced in male mice during the 3-day interval that immediately followed psilocybin administration. The effect of psilocybin on ethanol consumption was dose-related and was consistent across the 3-day interval at dosages of 0.5 mg/kg or greater. Psilocybin had no effect on consumption or preference when ethanol was subsequently reintroduced after 2 days of withdrawal. In contrast to males, psilocybin had no significant effect on ethanol consumption or preference in female mice at any dosage or time point. The lack of an effect of psilocybin on quinine preference, and its limited interaction with locomotor activity indicated that the observed reduction in voluntary ethanol consumption was not attributable to altered taste perception or motor effects. Total fluid consumption was increased in males at some time points and psilocybin dosages and unchanged in females, and the absence of any decrease in either group at any time point indicated that the observed reduction in ethanol consumption was not mediated by nonspecific effects on consummatory behavior. The finding of a sex-dependent effect of psilocybin on ethanol consumption suggests that the C57BL/6J mouse may provide a useful experimental approach to modeling sex differences in vulnerability to AUD in addition to investigation of the neurobiological basis of the effect of classical psychedelics on alcohol drinking behavior.

OBJECTIVES/OBJECTIVE:Disengagement from treatment is common in first episode schizophrenia (FES) and is associated with poor outcomes. Our aim was to determine whether hippocampal subfield volumes predict disengagement during maintenance treatment of FES. METHODS:FES patients were recruited from sites in Boston, New York, Shanghai, and Changsha. After stabilization on antipsychotic medication, participants were randomized to add-on citalopram or placebo and followed for 12 months. Demographic, clinical and cognitive factors at baseline were compared between completers and disengagers in addition to volumes of hippocampal subfields. RESULTS:Baseline data were available for 95 randomized participants. Disengagers (n = 38, 40%) differed from completers (n = 57, 60%) by race (more likely Black; less likely Asian) and in more alcohol use, parkinsonism, negative symptoms and more impairment in visual learning and working memory. Bilateral dentate gyrus (DG), CA1, CA2/3 and whole hippocampal volumes were significantly smaller in disengagers compared to completers. When all the eight volumes were entered into the model simultaneously, only left DG volume significantly predicted disengagement status and remained significant after adjusting for age, sex, race, intracranial volume, antipsychotic dose, duration of untreated psychosis, citalopram status, alcohol status, and smoking status (P < .01). Left DG volume predicted disengagement with 57% sensitivity and 83% specificity. CONCLUSIONS:Smaller left DG was significantly associated with disengagement status over 12 months of maintenance treatment in patients with FES participating in a randomized clinical trial. If replicated, these findings may provide a biomarker to identify patients at risk for disengagement and a potential target for interventions.

In neonatal brain development there is a period of normal apoptotic cell death that regulates adult neuron number. At approximately the same period, ethanol exposure can cause a dramatic spike in apoptotic cell death. While ethanol-induced apoptosis has been shown to reduce adult neuron number, questions remain about the regional selectivity of the ethanol effect, and whether the brain might have some capacity to overcome the initial neuron loss. The present study used stereological cell counting to compare cumulative neuron loss 8 h after postnatal day 7 (P7) ethanol treatment to that of animals left to mature to adulthood (P70). Across several brain regions we found that the reduction of total neuron number after 8 h was as large as that of adult animals. Comparison between regions revealed that some areas are more vulnerable, with neuron loss in the anterior thalamic nuclei > the medial septum/vertical diagonal band, dorsal subiculum, and dorsal lateral geniculate nucleus > the mammillary bodies and cingulate cortex > whole neocortex. In contrast to estimates of total neuron number, estimates of apoptotic cell number in Nissl-stained sections at 8 h after ethanol treatment provided a less reliable predictor of adult neuron loss. The findings show that ethanol-induced neonatal apoptosis often causes immediate neuron deficits that persist in adulthood, and furthermore suggests that the brain may have limited capacity to compensate for ethanol-induced neuron loss.

Introduction: Transitions between sleep and waking and sleep-dependent cortical oscillations are heavily dependent on GABAergic neurons. Importantly, GABAergic neurons are especially sensitive to developmental ethanol exposure, suggesting a potential unique vulnerability of sleep circuits to early ethanol. In fact, developmental ethanol exposure can produce long-lasting impairments in sleep, including increased sleep fragmentation and decreased delta wave amplitude. Here, we assessed the efficacy of optogenetic manipulations of somatostatin (SST) GABAergic neurons in the neocortex of adult mice exposed to saline or ethanol on P7, to modulate cortical slow-wave physiology. Methods: SST-cre × Ai32 mice, which selectively express channel rhodopsin in SST neurons, were exposed to ethanol or saline on P7. This line expressed similar developmental ethanol induced loss of SST cortical neurons and sleep impairments as C57BL/6By mice. As adults, optical fibers were implanted targeting the prefrontal cortex (PFC) and telemetry electrodes were implanted in the neocortex to monitor slow-wave activity and sleep-wake states. Results: Optical stimulation of PFC SST neurons evoked slow-wave potentials and long-latency single-unit excitation in saline treated mice but not in ethanol mice. Closed-loop optogenetic stimulation of PFC SST neuron activation on spontaneous slow-waves enhanced cortical delta oscillations, and this manipulation was more effective in saline mice than P7 ethanol mice. Discussion: Together, these results suggest that SST cortical neurons may contribute to slow-wave impairment after developmental ethanol.

Trauma exposure and post-traumatic stress disorder (PTSD) impact emotional and physical well-being, social functioning, and parent-child relationship quality. The effect of parental trauma on parenting and child maltreatment is often overlooked by current child welfare (CW) services. The novel intervention, Parenting-STAIR, was created to address maternal mental health, parenting skills, and child well-being outcomes. Parenting-STAIR is a combination of Skills Training in Affective and Interpersonal Regulation (STAIR) Narrative Therapy and Parent-Child Care (PC-CARE). This open pilot study aimed to examine the feasibility and preliminary impact of Parenting-STAIR in reducing maternal PTSD and increasing positive parenting skills for mothers and families involved in the child welfare system. Parenting-STAIR was delivered to 111 mothers receiving family preservation services in New York City. Of these, 70 completed treatment; statistical and clinically significant changes were observed for maternal PTSD and depression as well as in parenting stress, parenting skills, and child behaviors. These findings provide encouraging initial evidence for the feasibility and impact of this novel PTSD intervention. An evaluation of maltreatment recidivism is needed, as well as implementation of a randomized controlled trial to establish efficacy of the intervention.