Faculty Bibliography

Background: Reduced endocannabinoid "tone" has been posited in the pathophysiology of ASD animal models; children with ASD have been found to have lower peripheral endocannabinoid levels. Additionally, anecdotal reports suggest cannabinoids may be beneficial for some aspects of ASD.
Method(s): Double-blind placebo-controlled comparison (NCT02956226) of whole plant cannabis extract containing cannabidiol (CBD) and DELTA9-tetrahydrocannabinol (THC) in a 20:1 ratio and (2) purified CBD and THC in the same ratio. Participants were 150 children and adolescents with ASD, both males (80%) and females (mean age 11.8 +/-4.1 yrs). They received either placebo or cannabinoids for 12-weeks (testing efficacy) followed by a 4-week washout, and crossed-over to receive another treatment for 12 weeks to further assess tolerability.
Result(s): There were no treatment related severe or serious adverse events. None of the outcomes differed significantly between cannabinoid preparation, in either treatment period. Considering cannabinoids together, in the first period, 43% of 90 children who received cannabinoids were either much or very much improved on the CGI-I compared with 21% of 47 on placebo (p = 0.009). Placebo-cannabinoid differences were not significant on the other primary outcome, the Home Situations Questionnaire for ASD (HSQ-ASD). A positive response on the Social Responsiveness Scale-2 (SRS-2) was defined as 15% decrease or better from baseline. In the first treatment period, 44% of participants who received cannabinoids had a positive response compared with 19% on placebo (p = 0.013). In terms of possible mediators of treatment effects on the SRS-2, male sex and milder ASD symptoms at baseline were independently associated with better response to cannabinoid treatment.
Conclusion(s): Novel pharmacological treatments for the core and comorbid symptoms of ASD are urgently needed. Preclinical studies implicate the endocannabinoid system in the pathophysiology of ASD. In a controlled study of 150 children, a combination of CBD and THC, in a 20:1 ratio, either as a whole plant extract or as pure cannabinoids, improved disruptive behaviors and an index of ASD core symptoms, with relatively few adverse events. These data suggest that further investigation of cannabinoids in ASD is likely to be promising

Background: Serotonin and dopamine are neurotransmitters associated with multiple psychiatric disorders. How they interact during development to affect subsequent behavior remains unknown. Knockout of the serotonin transporter or administration of selective-serotonin-reuptake inhibitors (SSRIs) during early-life lead to novelty-induced exploration deficits in adulthood.
Method(s): Using a combination of optogenetics, behavioral testing and electrophysiology we tested the effects of perinatal exposure to fluoxetine (PN-FLX) on dopaminergic system's function in the adult. Between 10 to 15 mice per group, male and female, were administered with saline or fluoxetine (10 mg/kg IP) from P2 to P11. Mice were tested after 8 weeks of age.
Result(s): Here we show that Raphe nucleus serotonin neurons activate ventral tegmental area (VTA) dopamine neurons via glutamate cotransmission and that this cotransmission is impaired in postnatally SSRI treated animals. Moreover, we show that the SSRI-induced hypolocomotion is mimicked by blocking serotonin neuron glutamate cotransmission. Optogenetic activation of dopamine neurons rescued this hypolocomotor phenotype.
Conclusion(s): Our data demonstrate that serotonin neurons modulate dopaminergic activity via glutamate cotransmission and that this pathway is developmentally malleable, with high serotonin levels during early life blunting this capacity, resulting in reduced novelty-induced exploration in adulthood

BACKGROUND:Previous studies have documented the link between individual health behaviors and suicide, but little is known about the influence of health lifestyles on suicide among adolescents. This study aims to identify the unobserved patterns of health behaviors and to examine their associations with adolescent suicidal behaviors to inform screening of suicidality. METHODS:Data were derived from a nationally representative sample of adolescents (n = 14,506, ages 12-18, 50.9% female) in the national school-based 2017 Youth Risk Behavior Survey. Latent class analysis was performed based on 13 health behaviors related to diet (e.g., frequency of consuming breakfast, fruits/vegetables, soda), physical activity (frequencies of physical activity, sports team participation), sleep, and media use (TV/computers). Suicidal behaviors were measured by three dichotomized variables, including suicidal ideation, plan, and attempts. Multivariate logistic regressions were used to examine associations between identified classes and suicidal behaviors. RESULTS:Four classes of health lifestyles were identified. Class 1 (23.6%) consistently engaged in health-promoting behaviors, including eating breakfast daily, high intake of fruits/vegetables, physically active, and infrequent use of TV/computers. Class 2 (37.7%) had an irregular diet, moderate exercise, and high computer use. Class 3 (31.8%) had moderate diet, frequent exercise, and moderate sleep. Class 4 (6.9%) had the lowest engagement in health-promoting behaviors. Class 4 had higher odds of suicide plan than Class 1 (OR = 1.50, 95% CI = 1.10-2.05). Notably, Class 2 and 3 were less likely to attempt suicide than Class 1 (OR = 0.74, 95% CI = 0.57-0.95 for Class 2; OR = 0.65, 95% CI = 0.48-0.89 for Class 3). LIMITATIONS:Due to the cross-sectional design, no causal inference can be drawn. CONCLUSIONS:Both Class 1 (consistent) and Class 4 (lowest) engagement in health-promoting behaviors were associated with increased suicidal behaviors. Suicide prevention efforts that examine both lifestyles are keys to early detection of suicidal ideation and plans, and prevention of suicide attempts.

A lack or low level of social capital is associated with negative outcomes for communities impacted by poverty. However, less is known about how different types of social capital operate on the ground in poverty-impacted urban neighborhoods. This article explores the ways in which bonding, bridging, and linking capital manifest among residents of two poverty-impacted neighborhoods in New York City. Findings of the study reveal that urban neighborhood characteristics, more than individual-level factors, compromise the ability to develop and utilize the leveraging role of bridging and linking capital. Lack of safety resulted in limited trust, and involvement in community life limit bonding capital. Opportunities for bridging are restricted by the socioeconomically homogenous and spatially segregated nature of the communities. Linking capital is undermined by the lack of resources in the neighborhoods. These structural barriers prevent communities from breaking the cycle of poverty and should be explicitly targeted when developing interventions focused on building social capital.

Reports an error in "The World Health Organization Adult Attention-Deficit/Hyperactivity Disorder Self-Report Screening Scale for DSM-5" by Berk Ustun et al. (JAMA Psychiatry, 2017[May], Vol 74[5], 520-526). In the original article, there were errors in the footnote to Table 1 and in a corresponding section of Results. In Table 1 footnote a, the phrase "the highest scores are 5 for questions 1 and 2" should have read "the highest scores are 6 for question 3, 5 for questions 1 and 2," and the range given as "the range 0 of 24" should have been "in the range of 0 to 25." The corresponding 2 mentions in the Results of "0to 24" should have been "0to 25." This article was also corrected on October 25, 2017, to fix an error in Results. This article was corrected online. (The abstract of the original article appeared in record 2017-32659-009). Importance: Recognition that adult attention-deficit/hyperactivity disorder (ADHD) is common, seriously impairing, and usually undiagnosed has led to the development of adult ADHD screening scales for use in community, workplace, and primary care settings. However, these scales are all calibrated to DSM-IV criteria, which are narrower than the recently developed DSM-5 criteria. Objectives: To update for DSM-5 criteria and improve the operating characteristics of the widely used World Health Organization Adult ADHD Self-Report Scale (ASRS) for screening. Design, setting, and participants: Probability subsamples of participants in 2 general population surveys (2001-2003 household survey [n = 119] and 2004-2005 managed care subscriber survey [n = 218]) who completed the full 29-question self-report ASRS, with both subsamples over-sampling ASRS-screened positives, were blindly administered a semistructured research diagnostic interview for DSM-5 adult ADHD. In 2016, the Risk-Calibrated Supersparse Linear Integer Model, a novel machine-learning algorithm designed to create screening scales with optimal integer weights and limited numbers of screening questions, was applied to the pooled data to create a DSM-5 version of the ASRS screening scale. The accuracy of the new scale was then confirmed in an independent 2011-2012 clinical sample of patients seeking evaluation at the New York University Langone Medical Center Adult ADHD Program (NYU Langone) and 2015-2016 primary care controls (n = 300). Data analysis was conducted from April 4, 2016, to September 22, 2016. Main outcomes and measures: The sensitivity, specificity, area under the curve (AUC), and positive predictive value (PPV) of the revised ASRS. Results: Of the total 637 participants, 44 (37.0%) household survey respondents, 51 (23.4%) managed care respondents, and 173 (57.7%) NYU Langone respondents met DSM-5 criteria for adult ADHD in the semistructured diagnostic interview. Of the respondents who met DSM-5 criteria for adult ADHD, 123 were male (45.9%); mean (SD) age was 33.1 (11.4) years. A 6-question screening scale was found to be optimal in distinguishing cases from noncases in the first 2 samples. Operating characteristics were excellent at the diagnostic threshold in the weighted (to the 8.2% DSM-5/Adult ADHD Clinical Diagnostic Scale population prevalence) data (sensitivity, 91.4%; specificity, 96.0%; AUC, 0.94; PPV, 67.3%). Operating characteristics were similar despite a much higher prevalence (57.7%) when the scale was applied to the NYU Langone clinical sample (sensitivity, 91.9%; specificity, 74.0%; AUC, 0.83; PPV, 82.8%). Conclusions and relevance: The new ADHD screening scale is short, easily scored, detects the vast majority of general population cases at a threshold that also has high specificity and PPV, and could be used as a screening tool in specialty treatment settings.

The analysis of medical image time-series is becoming increasingly important as longitudinal imaging studies are maturing and large scale open imaging databases are becoming available. Image regression is widely used for several purposes: as a statistical representation for hypothesis testing, to bring clinical scores and images not acquired at the same time into temporal correspondence, or as a consistency filter to enforce temporal correlation. Geodesic image regression is the most prominent method, but the geodesic constraint limits the flexibility and therefore the application of the model, particularly when the observation time window is large or the anatomical changes are non-monotonic. In this paper, we propose to parameterize diffeomorphic flow by acceleration rather than velocity, as in the geodesic model. This results in a nonparametric image regression model which is completely flexible to capture complex change trajectories, while still constrained to be diffeomorphic and with a guarantee of temporal smoothness. We demonstrate the application of our model on synthetic 2D images as well as real 3D images of the cardiac cycle.

OBJECTIVE:This study describes the experiences of adult psychiatry residents working in an established faculty-led asylum clinic within a community-based, academic residency program at the Cambridge Health Alliance. METHODS:Eighteen psychiatry residents who participated in the asylum clinic were sent electronic surveys asking about their background and experience. Respondents' responses were collected anonymously. RESULTS:Sixteen out of 18 (89%) trainees responded. Thirteen respondents had a personal history with immigration. Fifty-three percent of residents wanted to utilize their professional standing to advance moral good. Writing up affidavits was noted to be challenging by nine (60%) of 15 trainees. Ninety-four percent (15/16) of trainees noted that they would be willing to perform future evaluations. Most noted that performing evaluations had a significant impact on their clinical practice and their conceptualization of their own roles as psychiatrists. CONCLUSIONS:Participating in asylum evaluations impacts residents' sense of themselves as psychiatrists and expands their views about psychiatrists' roles.

Background: Symptoms related to impaired visuospatial function are relatively common in patients with Parkinson's disease (PD). Restricted visual processing can directly hamper patients' motor function. For example, systematic biases in visual perception may influence navigational veering, thus directly affecting locomotion. In patients with PD, an impaired visual function is linked to negative feelings including depression, fearfulness and reduced self-efficacy. Art Therapy (AT) has the potential of recruiting different neural networks, including those concerned with high visual conscious perception. As such, AT may serve as a neurobehavioral intervention to improve multiple functional domains, including visuospatial functions and emotional wellness.
Method(s): This is a dual-phase exploratory study. 1: cross-sectional, controlled, biomarker study on 30 non-demented PD patients (H&Y 2-3) and 30 age-matched controls; 2: prospective, open label study involving 20 sessions of AT (2sessions/week). Motor and gait functions were assessed by MDS-UPDRS, Timed Up and Go test (TUG), and wearable accelerometers. Cognitive and Visuospatial functions were assessed by neuropsychological inventories (MoCA, Rey-Osterrieth FigureTest, Benton Visual Test), computerized testing (Navon VisualTest, Visual Research Test, and visual reaction time), and binocular eyetracking (Eyelink 2). Psychological wellness was assessed by Beck Depression Index (BDI), Modified Fatigue Impact Scale, and PROMIS-Self-Efficacy scales. Brain imaging included T1-weighted 3D high resolution, DWI, and RSfMRI sequences. Preliminary analyses were conducted on clinical data from 18 PD-patients and 14 controls completing the study. Eye tracking from 4 subjects was analyzed for exploratory purposes.
Result(s): PD-patients and controls were significantly different with respect to BDI score, Navon Visual Test, Rey Figure Test, UPDRSIII, and TUG-3 (maximum gait speed). Following AT, PD patients showed significant improvements in UPDRS-III, UPDRS-total, PROMIS (symptoms management), and Navon Visual Test (number of errors). A strong trend towards improved ReyeFigureTest was observed. On eye tracking analysis, significant increases in exploratory eye movements and fixation patterns were observed spatiotopically during examined stimulus regions.
Discussion(s): According to our preliminary findings, AT may improve visual-constructional abilities, visual recognition, and motor function. These improvements are accompanied by increased self-efficacy and changes in oculomotor behavior characterized by a more efficient visual exploration strategy. The duration of these potential benefits as well as their underlying mechanisms remain to be determined