Faculty Bibliography

BACKGROUND:Oxytocin is a peptide hormone that influences the integration of social cognition with behavior and affect regulation. Oxytocin also prominently directs the transition of neuronal GABA neurotransmission from excitatory to inhibitory after birth. The oxytocin receptor (OXTR) is linked to schizophrenia, a heterogeneous syndrome. Relationships of OXTR polymorphisms with specific clinical features could aid in evaluating any role of oxytocin in the pathogenesis of schizophrenia. METHOD/METHODS:Schizophrenia cases with rare missense coding OXTR single nucleotide variants (SNVs) were identified from a well-characterized sample of cases and controls who were assessed for symptoms, cognition and early life trauma. RESULTS:Five of 48 cases showed rare OXTR variants. Compared to the other cases they had less severe negative symptoms (deficits in emotional expression and motivation) and less severe general psychopathology scores (depression and anxiety). They demonstrated lower nonverbal (performance) than verbal intelligence due to deficient perceptual organization and slow processing speed. They also reported greater early trauma exposure (physical and sexual abuse and emotional trauma). CONCLUSION/CONCLUSIONS:Cases carrying rare OXTR SNVs had less negative and affective symptoms than other cases, but similar psychotic symptoms, along with specific cognitive deficits. The clinical characterization of these cases occurred in association with environmental exposure to early trauma, especially sexual abuse, which may have influenced the expression of schizophrenia in subjects harboring specific SNVs in the OXTR.

Background/UNASSIGNED:The aim of this study was to compare the relationship between core executive functions and frontoparietal network connections at rest between children who had suffered an arterial ischemic stroke and typically developing peers. Methods/UNASSIGNED:Children diagnosed with arterial ischemic stroke more than two years previously and typically developing controls were included. Executive function (EF) measures comprised inhibition (Go-NoGo task), fluency (category fluency task), processing speed (processing speed tasks), divided attention, working memory (letter-number sequencing), conceptual reasoning (matrices) and EF in everyday life (questionnaire). High-resolution T1-weighted magnetic resonance (MR) structural images and resting-state functional MR imaging were acquired. Independent component analysis was used to identify the frontoparietal network. Functional connections were obtained through correlation matrices; associations between cognitive measures and functional connections through Pearson's correlations. Results/UNASSIGNED:Twenty participants after stroke (7 females; mean age 16.0 years) and 22 controls (13 females; mean age 14.8 years) were examined. Patients and controls performed within the normal range in all executive tasks. Patients who had had a stroke performed significantly less well in tests of fluency, processing speed and conceptual reasoning than controls. Resting-state functional connectivity between the left and right inferior parietal lobe was significantly reduced in patients after pediatric stroke. Fluency, processing speed and perceptual reasoning correlated positively with the interhemispheric inferior parietal lobe connection in patients and controls. Conclusion/UNASSIGNED:Decreased interhemispheric connections after stroke in childhood may indicate a disruption of typical interhemispheric interactions relating to executive functions. The present results emphasize the relationship between functional organization of the brain at rest and cognitive processes.

BACKGROUND:Autism spectrum disorder (ASD) is a mental disorder that has long been considered to result from brain underconnectivity. However, volumetric analysis of structural MRI data has failed to find consistent white matter alterations in patients with ASD. The present study aims to examine whether there are consistent focal white matter alterations as measured by diffusion tensor imaging (DTI) in individuals with ASD compared with typically developing (TD) individuals. METHOD/METHODS:Coordinate-based meta-analysis was performed on 14 studies that reported fractional anisotropy (FA) alterations between individuals with ASD and TD individuals. These studies have in total 297 subjects with ASD and 302 TD subjects. RESULTS:Activation likelihood estimation (ALE) analysis identified two clusters of white matter regions that showed consistent reduction of FA in individuals with ASD compared with TD individuals: the left splenium of corpus callosum and the right cerebral peduncle. CONCLUSIONS:Consistent focal white matter reductions in ASD could be identified by using FA, highlighting the cerebral peduncle which is usually overlooked in studies focusing on major white matter tracts. These focal reductions in the splenium and the cerebral peduncle may be associated with sensorimotor impairments seen in individuals with ASD.

Cognitive deficits have an important role in the neurodevelopment of schizophrenia and other psychotic disorders. However, there is a continuing debate as to whether cognitive impairments in the psychosis prodrome are stable predictors of eventual psychosis or undergo a decline due to the onset of psychosis. In the present study, to determine how cognition changes as illness emerges, we examined baseline neurocognitive performance in a large sample of helping-seeking youth ranging in clinical state from low-risk for psychosis through individuals at clinical high-risk (CHR) for illness to early first-episode patients (EFEP). At baseline, the MATRICS Cognitive Consensus battery was administered to 322 individuals (205 CHRs, 28 EFEPs, and 89 help-seeking controls, HSC) that were part of the larger Early Detection, Intervention and Prevention of Psychosis Program study. CHR individuals were further divided into those who did (CHR-T; n = 12, 6.8%) and did not (CHR-NT, n = 163) convert to psychosis over follow-up (Mean = 99.20 weeks, SD = 21.54). ANCOVAs revealed that there were significant overall group differences (CHR, EFEP, HSC) in processing speed, verbal learning, and overall neurocognition, relative to healthy controls (CNTL). In addition, the CHR-NTs performed similarly to the HSC group, with mild to moderate cognitive deficits relative to the CTRL group. The CHR-Ts mirrored the EFEP group, with large deficits in processing speed, working memory, attention/vigilance, and verbal learning (>1 SD below CNTLs). Interestingly, only verbal learning impairments predicted transition to psychosis, when adjusting for age, education, symptoms, antipsychotic medication, and neurocognitive performance in the other domains. Our findings suggest that large neurocognitive deficits are present prior to illness onset and represent vulnerability markers for psychosis. The results of this study further reinforce that verbal learning should be specifically targeted for preventive intervention for psychosis.

We examine the impact of mental health based primary care on physical health treatment among community mental health center patients in New York State using propensity score adjusted difference in difference models. Outcomes are quality indicators related to outpatient medical visits, diabetes HbA1c monitoring, and metabolic monitoring of antipsychotic treatment. Results suggest the program improved metabolic monitoring for patients on antipsychotics in one of two waves, but did not impact other quality indicators. Ceiling effects may have limited program impacts. More structured clinical programs to may be required to achieve improvements in quality of physical health care for this population.

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.

Sleep alterations associated with adulthood ADHD are poorly understood. Here, we conducted the first meta-analysis of sleep studies in adults with ADHD. Based on a pre-registered protocol (PROSPERO-CRD42017065407), we searched Pubmed, Ovid and Web of Knowledge databases through August 3rd, 2017, with no language or publication type restrictions, and contacted study authors for unpublished data/information. From a pool of 8812 references, we retained 13 studies. Random-effects models were performed and study quality was rated using the Newcastle-Ottawa Scale. Compared to adults without ADHD, those with ADHD significantly differed in seven out of nine subjective parameters (Standardized Mean Difference, SMD, ranging from 0.56 to 1.55) and two out of five actigraphic parameters [SMD (95% CI): sleep onset latency: 0.80 (0.46-1.14); sleep efficiency: -0.68 (-1.03, -0.34)]. No significant differences were detected for polysomnographic parameters. We conclude that, whereas subjectively reported sleep problems are significantly associated with ADHD in adults and should be systematically screened during the clinical interview, additional research is needed to understand if they are underpinned by objective sleep alterations.

OBJECTIVE:There is limited research on metabolic abnormalities in psychotropic-naïve patients with serious mental illness (SMI). Our study examined metabolic conditions in a large, ethnically diverse sample of psychotropic-naïve and non-naïve adults with SMI at an urban public hospital. METHODS:In this cross-sectional study of 923 subjects, the prevalences of hyperglycemia meeting criteria for type 2 diabetes mellitus (T2DM) based on fasting plasma glucose and obesity defined by BMI and abdominal girth were compared across duration of psychotropic medication exposure. Multiple logistic regression models used hyperglycemia and obesity as dependent variables and age, sex, race/ethnicity, and years on psychotropics as independent variables. RESULTS:Psychotropic-naïve patients, including both schizophrenia and non-psychotic subgroups, showed an elevated prevalence of hyperglycemia meeting criteria for T2DM and a decreased prevalence of obesity compared to the general population. Obesity rates significantly increased for those on psychotropic medications more than 5 years, particularly for patients without psychosis (BMI: aOR = 5.23 CI = 1.44-19.07; abdominal girth: aOR = 6.40 CI = 1.98-20.69). Women had a significantly higher obesity rate than men (BMI: aOR = 1.63 CI = 1.17-2.28; abdominal girth: aOR = 3.86 CI = 2.75-5.44). Asians had twice the prevalence of hyperglycemia as whites (aOR = 2.29 CI = 1.43-3.67), despite having significantly less obesity (BMI: aOR = .39 CI = .20-.76; abdominal girth: aOR = .34 CI = .20-.60). Hispanics had a higher rate of obesity by BMI than whites (aOR = 1.91 CI = 1.22-2.99). CONCLUSIONS:This study showed disparities between obesity and T2DM in psychotropic-naïve patients with SMI, suggesting separate risk pathways for these two metabolic conditions.

BACKGROUND:Concerns about antipsychotic prescribing for children, particularly those enrolled in Medicaid and with Supplemental Security Income (SSI), continue despite recent calls for selective use within established guidelines. OBJECTIVES/OBJECTIVE:To (a) examine the application of 6 quality measures for antipsychotic medication prescribing in children and adolescents receiving Medicaid and (b) understand distinctive patterns across eligibility categories in order to inform ongoing quality management efforts to support judicious antipsychotic use. METHODS:Using data for 10 states from the 2008 Medicaid Analytic Extract (MAX), a cross-sectional assessment of 144,200 Medicaid beneficiaries aged < 21 years who received antipsychotics was conducted to calculate the prevalence of 6 quality measures for antipsychotic medication management, which were developed in 2012-2014 by the National Collaborative for Innovation in Quality Measurement. These measures addressed antipsychotic polypharmacy, higher-than-recommended doses of antipsychotics, use of psychosocial services before antipsychotic initiation, follow-up after initiation, baseline metabolic screening, and ongoing metabolic monitoring. RESULTS:Compared with children eligble for income-based Medicaid, children receiving SSI and in foster care were twice as likely to receive higher-than-recommended doses of antipsychotics (adjusted odds ratio [AOR] = 2.4, 95% CI = 2.3-2.6; AOR = 2.5, 95% CI = 2.4-2.6, respectively) and multiple concurrent antipsychotic medications (AOR = 2.2, 95% CI = 2.0-2.4; AOR = 2.2, 95% CI = 2.0-2.4, respectively). However, children receiving SSI and in foster care were more likely to have appropriate management, including psychosocial visits before initiating antipsychotic treatment and ongoing metabolic monitoring. While children in foster care were more likely to experience baseline metabolic screening, SSI children were no more likely than children eligible for income-based aid to receive baseline screening. CONCLUSIONS:While indicators of overuse were more common in SSI and foster care groups, access to follow-up, metabolic monitoring, and psychosocial services was somewhat better for these children. However, substantial quality shortfalls existed for all groups, particularly metabolic screening and monitoring. Renewed efforts are needed to improve antipsychotic medication management for all children. DISCLOSURES/UNASSIGNED:This project was supported by grant number U18HS020503 from the Agency for Healthcare Research and Quality (AHRQ) and Centers for Medicare & Medicaid Services (CMS). Additional support for Rutgers-based participants was provided from AHRQ grants R18 HS019937 and U19HS021112, as well as the New York State Office of Mental Health. The content of this study is solely the responsibility of the authors and does not necessarily represent the official views of AHRQ, CMS, or the New York State Office of Mental Health. Finnerty has been the principle investigator on research grants/contracts from Bristol Myers Squibb and Sunovion, but her time on these projects is fully supported by the New York State Office of Mental Health. Scholle, Byron, and Morden work for the National Committee for Quality Assurance, a not-for-profit organization that develops and maintains quality measures. Neese-Todd was at Rutgers University at the time of this study and is now employed by the National Committee for Quality Assurance. The other authors have no financial relationships relevant to this article to disclose. Study concept and design were contributed by Finnerty, Neese-Todd, and Crystal, assisted by Scholle, Leckman-Westin, Horowitz, and Hoagwood. Scholle, Byron, Morden, and Hoagwood collected the data, and data interpretation was performed by Pritam, Bilder, Leckman-Westin, and Finnerty, with assistance from Scholle, Byron, Crystal, Kealey, and Neese-Todd. The manuscript was written by Leckman-Westin, Kealey, and Horowitz and revised by Layman, Crystal, Leckman-Westin, Finnerty, Scholle, Neese-Todd, and Horowitz, along with the other authors.