Faculty Bibliography

Purpose of Study Autism spectrum disorders (ASDs) are neurodevelopmental disorders with lifelong consequences and poorly understood pathophysiology. Dysregulated cholesterol metabolism is implicated in ASD etiology. Cholesterol is essential for neuroactive steroid production, myelin sheath formation, and normal brain development. Early postnatal or in utero exposure to the antiepileptic drug valproic acid (VPA), a branched short-chain fatty acid, causes autism-like neural and behavioral deficits in humans and rodents. This study examines the link between VPA and cholesterol deficit in cultured human neurons and microglia. Methods Used SHSY-5Y human neuroblastoma cells and HMC3 human microglial cells were exposed to VPA at 0, 250, 1000 and 5000 muM for 24h, N=3 per condition. Expression of critical genes that regulate cholesterol transport were quantified by RT-PCR using specific primers for each. These include the efflux proteins ABCA1, ABCG1, 27-hydroxylase (27-OHase) and 24-hydroxylase (24-OHase), and the influx scavenger receptor CD36 - all vital for brain cholesterol balance. Expression of these target genes was normalized to concurrently measured GAPDH mRNA levels. Summary of Results In SH-SY5Y neurons, VPA exposure caused a concentration-dependent increase in ABCA1 (P <0.001), ABCG1, 27-OHase (P <0.001) (figure 1), and CD36 (P=0.015). In HMC3, VPA exposure caused a concentration- dependent increase in ABCG1 (80-fold at highest dose, P<=0.001) and 24-OHase (P < 0.001) with a reduction in ABCA-1 (P=0.002) and an increase in CD36 (P<0.001). Conclusions This study shows that VPA has a dramatic hypocholesterolemic effect on two key cell types that compose the developing brain. The net impact of the changes observed in these cholesterol-related genes would be outflow and metabolism. Further, enhanced 27-OHase activity produces an oxysterol metabolite with neurotoxic effects that include downregulating synaptic proteins and decreasing neurite number and length. Together, our results suggest that VPA impairs brain cholesterol homeostasis. A better understanding of the involvement of cholesterol in the mechanisms by which VPA leads to ASDs may translate into novel preventative therapies for this serious disorder

This editorial looks at the current state of the integration of medicine and psychiatry in clinical practice. We note selected recent triumphs and barriers to implementing integrated care, highlighting some gaps and priorities for future innovations. In contrast to the relatively more orderly culture of health services research, where some notable innovations in integrated care were funded, tested, and published, the health care marketplace can be a difficult place to identify and track the innovations that could shape health care reform. Recognizing the need to find, describe, and disseminate the most innovative models in integrated care, the Association of Medicine and Psychiatry (AMP) launched in 2016 the Innovative Models for Integrated Care Awards. Although many service innovations solve local problems, some can also act as models to be adopted in multiple settings. The projects that win AMP Innovative Models for Integrated Care Awards are selected for their innovativeness, their clinical importance, their generalizability, and their effectiveness. We briefly describe here the four models that earned these awards at the 2017 AMP Annual Meeting. They demonstrate innovations across a range of settings and populations: inpatient general hospital patients under constant observation in New York, severely mentally ill patients in a federally qualified health center in San Francisco, outpatients in a VA women's health center in Chicago, and HIV patients in an academic infectious disease clinic in Charleston, south Carolina. These model descriptions aim to encourage the implementation of innovative models that advance the integration of medicine and psychiatry.

Psychosis is a relatively common psychiatric phenomenon seen in patients with Prader-Willi Syndrome (PWS). However, the presentation is atypical and difficult to classify within currently defined affective or psychotic disorders. This distinct presentation may be better understood as a phenomenon called "cycloid psychosis," described as an episodic psychosis with rapid full recovery between episodes. This study retrospectively analyzed the cases of 12 patients with genetically confirmed PWS who presented to an ambulatory psychiatric center for a change in behavior consistent with psychosis. Each case was then assessed for symptoms of cycloid psychosis, bipolar disorder, depression with psychotic features, schizophrenia, and schizoaffective disorder. Out of the 12 patients, 11 (91.7%) met the currently described diagnostic criteria for cycloid psychosis. Of the 12 patients, 7 (58.3%) also met the diagnostic criteria for bipolar disorder, and 1 (8.3%) also met the diagnostic criteria for schizoaffective disorder. None of the patients met the criteria for schizophrenia or depression with psychotic features. The findings in this study suggest that cycloid psychosis and bipolar disorder may both be comorbid with PWS. Psychiatric comorbidities in patients with PWS are atypical and clinicians should be aware of conditions such as cycloid psychosis when managing this vulnerable population.

OBJECTIVE:To examine the role of Guanfacine Extended Release (GXR) in the management of behavioral disturbances in patients with Prader-Willi Syndrome (PWS). METHODS:Twenty from a total of 27 individuals with genetically confirmed PWS, 6-26 years of age, with the following symptoms were identified: significant aggression/agitation, skin picking, and/or symptoms of attention-deficit/hyperactivity disorder (ADHD). Response to GXR for the above noted symptoms was categorized as improved, worsened, or unchanged, while assessing for side effects and tolerability. RESULTS:Eleven of the 20 individuals reported skin-picking, 17 reported aggression/agitation, and 16 reported symptoms of ADHD. Nine (81.8%), 14 (82.3%), and 15 (93.7%) individuals showed an improvement in skin-picking, aggression/agitation, and ADHD, respectively, while on GXR treatment. Two patients with prior complaints of psychotic symptoms did not respond to GXR. Of note, no abnormal weight gain or significant adverse reaction was observed in this group, while on GXR. CONCLUSIONS:In this study, GXR demonstrated improvement in symptoms of skin picking, aggression/agitation, and ADHD in patients with PWS. GXR was not effective in reducing psychosis or agitation related to psychotic symptoms. Future studies are warranted to further establish the utility of GXR in PWS patients.

OBJECTIVE:/UNASSIGNED:ALPIM (anxiety, laxity, pain, immune, and mood) syndrome has been previously described in adults. The authors aimed to identify its occurrence in adolescents and confirm its existence in adults. Given the association of the disorder with somatic symptoms, separation anxiety disorder (SAD) was explored as an ALPIM comorbidity. METHODS:/UNASSIGNED:Medical records of patients aged 11-34 with a diagnosis of depression or anxiety (panic disorder, SAD, social anxiety or generalized anxiety disorder) seen during a 1-year period were reviewed. Data were collected on the presence of ALPIM comorbidities. Analyses were conducted to detect their co-occurrence and evaluate possible predictors of the ALPIM syndrome. RESULTS:/UNASSIGNED:Inclusion criteria were met by 185 patient charts. A significant association was observed between the ALPIM comorbidities with 20 study subjects (10.8%) meeting criteria for ALPIM syndrome (patients with one or more diagnoses from each ALPIM domain). Patients with SAD had increased odds of being diagnosed with ALPIM (odds ratio=7.14, 95% CI=2.48-20.54, p<0.001). Neither major depression nor generalized anxiety disorder was found to be predictive of ALPIM syndrome. There was no difference in the prevalence of ALPIM-related comorbidities between study subjects <18 years old compared with those ≥18 years old. CONCLUSIONS:/UNASSIGNED:These findings reestablish the association of distinct psychiatric and nonpsychiatric conditions described as the ALPIM syndrome. Furthermore, the syndrome may present during adolescence. SAD may be an independent predictive factor for the occurrence of ALPIM syndrome. Patients with individual ALPIM comorbidities should be assessed for the syndrome, especially if they have a history of SAD.

Constant observation (CO) is a common economic burden on general hospitals. A quality improvement (QI) project focusing on behavioral health (BH) management of this population was piloted using a novel BH protocol for the proactive assessment and management of all patients requiring CO. The impact on CO-cost and length of stay (LOS) was assessed. Data on demographics, diagnoses, psychopharmacologic treatment, complications and clinical setting were collected and analyzed for all CO-patients over a 6-month period. Cost and LOS data were compared with a similar sequential group prior to project implementation. Out of the 533 patients requiring CO during the study period, 491 underwent the protocol. This QI-project resulted in a significant reduction in the average monthly CO-cost by 33.06% and a 15% reduction in LOS without any increase in complications.

In hospitals, use of constant observation (CO) causes significant economic burden without demonstrated reduction in adverse events. A novel quality improvement (QI) project was developed to reduce use of CO by integrating proactive behavioral health management of all patients requiring CO in a general hospital. Specific nonpharmacologic and pharmacologic interventions used in this project, which included 491 patients, are discussed. Data collected were compared with data from a baseline period before project implementation. The average monthly cost of observers was reduced by 33%, and length of stay was reduced 15% without increased complications. Using QI to develop proactive and consistent involvement of a designated behavioral health team and potentially reproducible care protocols for patients requiring CO resulted in improvement in quality, reduction in cost, and enhanced behavioral health integration in the general hospital.