Vitamin D levels among adult psychiatric inpatients and the association with psychosis.

BACKGROUND: The association between low vitamin D levels and mental illness has been described in earlier research. The aim of our study was to examine the association between vitamin D levels with psychotic symptoms among hospitalized patients. METHODS: A total of 1,456 patient records from an academic psychiatric hospital were examined. Vitamin D levels were classified as normal (>30 ng/mL); insufficient (20 to 30 ng/mL); and deficient (<20 ng/mL). We then analyzed the association among vitamin D groups and symptoms of psychosis. RESULTS: The average vitamin D level in our sample was 23.59 ng/mL, with 76.2% of patients presenting with vitamin D levels <30 ng/mL. There was a significant association between vitamin D levels <20 ng/mL and symptoms of psychosis (P < .05). African American patients had lower mean vitamin D levels than White patients (15.6 ± 0.2 ng/mL vs 25.8 ± 0.4 ng/mL, P < .001). There was no sex difference in vitamin D levels (females: 23.3 ± 11.5 ng/mL; males: 23.9 ± 11.0 ng/mL). CONCLUSIONS: Patients with vitamin D levels <30 ng/mL were 1.5 times more likely to have symptoms of psychosis. Patients who were African American, Hispanic, Asian, or biracial had lower vitamin D levels than patients who were White. Multivariate analysis found that after adjusting for age, sex, and race, the association between vitamin D and psychosis was not statistically significant. Possible explanations could include the known tendency to overdiagnose psychosis among individuals who are African American, referral bias, subgroup effect, or an epiphenomenon.

Assessment of Virtual Mindfulness-Based Training for Health Care Professionals: Improved Self-Reported Respiration Rates, Perceived Stress, and Resilience.

Background: Mindfulness in Motion (MIM) is a workplace resilience-building intervention that has shown reductions in perceived stress and burnout, as well as increased resilience and work engagement in health care workers. Objective: To evaluate effects of MIM delivered in a synchronous virtual format on self-reported respiratory rates (RR), as well as perceived stress and resiliency of health care workers. Methods: Breath counts were self-reported by 275 participants before and after 8 weekly MIM sessions. MIM was delivered virtually in a group format as a structured, evidence-based workplace intervention including a variety of mindfulness, relaxation, and resilience-building techniques. Participants counted their breaths for 30 seconds, which was then multiplied by 2 to report RR. Additionally, participants completed Perceived Stress Scale and Connor-Davidson Resiliency Scale. Results: According to mixed effect analyses there were main effects of MIM Session (P < .001) and Weeks (P < .001), but no Session by Week interaction (P = .489) on RR. On average, RR prior to MIM sessions were reduced from 13.24 bpm (95% CI = 12.94, 13.55 bpm) to 9.69 bpm (95% CI = 9.39, 9.99 bpm). When comparing average Pre-MIM and Post-MIM RR throughout the MIM intervention, Week-2 (mean = 12.34; 95% CI = 11.89, 12.79 bpm) was not significantly different than Week-1 (mean = 12.78; 95% CI = 12.34, 13.23 bpm), but Week-3 through Week-8 demonstrated significantly lower average Pre-MIM and Post-MIM RR compared to Week-1 (average weekly difference range: 1.36 to 2.48 bpm, P < .05). Perceived stress was reduced from Week-1 (17.52 ± 6.25) to after Week-8 (13.52 ± 6.04; P < .001), while perceived resiliency was increased from Week-1 (11.30 ± 5.14) to after Week-8 (19.29 ± 2.58); P < .001). Conclusion: Thus far, completion of MIM sessions has shown acute and long-term effects on self-reported RR, but more research is required to determine the extent of improved parasympathetic (relaxed) states. Collectively, this work has shown value for mind-body stress mitigation and resiliency-building in high stress acute health care environments.

Neurodegenerative Diseases: From Dysproteostasis, Altered Calcium Signalosome to Selective Neuronal Vulnerability to AAV-Mediated Gene Therapy.

Despite intense research into the multifaceted etiology of neurodegenerative diseases (ND), they remain incurable. Here we provide a brief overview of several major ND and explore novel therapeutic approaches. Although the cause (s) of ND are not fully understood, the accumulation of misfolded/aggregated proteins in the brain is a common pathological feature. This aggregation may initiate disruption of Ca++ signaling, which is an early pathological event leading to altered dendritic structure, neuronal dysfunction, and cell death. Presently, ND gene therapies remain unidimensional, elusive, and limited to modifying one pathological feature while ignoring others. Considering the complexity of signaling cascades in ND, we discuss emerging therapeutic concepts and suggest that deciphering the molecular mechanisms involved in dendritic pathology may broaden the phenotypic spectrum of ND treatment. An innovative multiplexed gene transfer strategy that employs silencing and/or over-expressing multiple effectors could preserve vulnerable neurons before they are lost. Such therapeutic approaches may extend brain health span and ameliorate burdensome chronic disease states.

Faculty Self-Evaluation of Experiences with Delivering Feedback to Trainees Across Academic Ranks.

BACKGROUND: The ability to provide feedback is a developable faculty skill; however, it is unclear how academic rank impacts experiences with feedback delivery. METHODS: A survey was distributed to 1258 physicians of all academic ranks at a large academic medical center. Questions explored the respondent's feedback delivery beliefs and barriers. RESULTS: In total, 96% of respondents agreed feedback is important to resident education. Higher academic rank correlated with increased comfort with feedback delivery, and 89% of respondents experienced at least 1 barrier to feedback delivery. CONCLUSION: Feedback experiences vary across academic ranks, with full professors being more comfortable with feedback delivery and less likely to experience barriers. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40670-020-01196-5.

Intellectual disability: dendritic anomalies and emerging genetic perspectives.

Intellectual disability (ID) corresponds to several neurodevelopmental disorders of heterogeneous origin in which cognitive deficits are commonly associated with abnormalities of dendrites and dendritic spines. These histological changes in the brain serve as a proxy for underlying deficits in neuronal network connectivity, mostly a result of genetic factors. Historically, chromosomal abnormalities have been reported by conventional karyotyping, targeted fluorescence in situ hybridization (FISH), and chromosomal microarray analysis. More recently, cytogenomic mapping, whole-exome sequencing, and bioinformatic mining have led to the identification of novel candidate genes, including genes involved in neuritogenesis, dendrite maintenance, and synaptic plasticity. Greater understanding of the roles of these putative ID genes and their functional interactions might boost investigations into determining the plausible link between cellular and behavioral alterations as well as the mechanisms contributing to the cognitive impairment observed in ID. Genetic data combined with histological abnormalities, clinical presentation, and transgenic animal models provide support for the primacy of dysregulation in dendrite structure and function as the basis for the cognitive deficits observed in ID. In this review, we highlight the importance of dendrite pathophysiology in the etiologies of four prototypical ID syndromes, namely Down Syndrome (DS), Rett Syndrome (RTT), Digeorge Syndrome (DGS) and Fragile X Syndrome (FXS). Clinical characteristics of ID have also been reported in individuals with deletions in the long arm of chromosome 10 (the q26.2/q26.3), a region containing the gene for the collapsin response mediator protein 3 (CRMP3), also known as dihydropyrimidinase-related protein-4 (DRP-4, DPYSL4), which is involved in dendritogenesis. Following a discussion of clinical and genetic findings in these syndromes and their preclinical animal models, we lionize CRMP3/DPYSL4 as a novel candidate gene for ID that may be ripe for therapeutic intervention.

Collapsin Response Mediator Proteins: Novel Targets for Alzheimer's Disease.

Numerous experimental and postmortem studies have increasingly reported dystrophic axons and dendrites, and alterations of dendritic spine morphology and density in the hippocampus as prominent changes in the early stages of Alzheimer's disease (AD). Furthermore, these alterations tend to correlate well with the progressive cognitive decline observed in AD. For these reasons, and because these neurite structures have a capacity to re-grow, re-establish lost connections, and are critical for learning and memory, there is compelling evidence to suggest that therapeutic interventions aimed at preventing their degradation or promoting their regrowth may hold tremendous promise in preventing the progression of AD. In this regard, collapsin response mediator proteins (CRMPs), a family of phosphoproteins playing a major role in axon guidance and dendritic growth, are especially interesting. The roles these proteins play in neurons and immune cells are reviewed here.

Formalizing Feedback: Introducing a Structured Approach in an Outpatient Resident Clinic.

OBJECTIVE: Delivering feedback is an integral part of graduate medical education. This paper will present how feedback research informed the development of a new feedback model and discuss its implementation and evaluation by residents in an outpatient psychiatry clinic. METHOD: After reviewing research, a new feedback model of self-determined goal setting with guided objectives and quarterly formal in-person feedback sessions was implemented with 10 psychiatry residents during their 12-month outpatient experience in postgraduate year (PGY)-3. Residents received a pre-intervention survey to assess existing opinions of feedback and goal setting and a post-intervention survey to evaluate experiences with the new feedback model. RESULTS: On the pre-intervention survey, 3 of 8 resident respondents indicated they had previously set goals, and only 4 of 8 predicted goal setting would be helpful, with average helpfulness rating of 3.62 (scale of 1 to 5). Cumulatively, 10 PGY-3 residents set 31 goals over the academic year. On the post-intervention survey, resident respondents rated the helpfulness of goal setting at 4.71 and quarterly, formal, in-person feedback meetings at 4.86. Success at reaching their self-determined goals was rated at 5 by all respondents. CONCLUSIONS: Utilizing self-determined goals and formal in-person feedback sessions seemed to provide the framework for an effective feedback model in an outpatient resident clinic. This pilot project suggests that introducing formal feedback models can have a positive impact on resident clinical and educational growth. The data support expanding the model to assess its generalizability with the goal of furthering development of evidence-based feedback models.

Opposing Morphogenetic Defects on Dendrites and Mossy Fibers of Dentate Granular Neurons in CRMP3-Deficient Mice.

Collapsin response mediator proteins (CRMPs) are highly expressed in the brain during early postnatal development and continue to be present in specific regions into adulthood, especially in areas with extensive neuronal plasticity including the hippocampus. They are found in the axons and dendrites of neurons wherein they contribute to specific signaling mechanisms involved in the regulation of axonal and dendritic development/maintenance. We previously identified CRMP3's role on the morphology of hippocampal CA1 pyramidal dendrites and hippocampus-dependent functions. Our focus here was to further analyze its role in the dentate gyrus where it is highly expressed during development and in adults. On the basis of our new findings, it appears that CRMP3 has critical roles both in axonal and dendritic morphogenesis of dentate granular neurons. In CRMP3-deficient mice, the dendrites become dystrophic while the infrapyramidal bundle of the mossy fiber shows aberrant extension into the stratum oriens of CA3. This axonal misguided projection of granular neurons suggests that the mossy fiber-CA3 synaptic transmission, important for the evoked propagation of the activity of the hippocampal trisynaptic circuitry, may be altered, whereas the dystrophic dendrites may impair the dynamic interactions with the entorhinal cortex, both expected to affect hippocampal function.

Feasibility of a Mindfulness-Based Intervention for Surgical Intensive Care Unit Personnel.

BACKGROUND: Surgical intensive care unit personnel are exposed to catastrophic situations as they care for seriously injured or ill patients. Few interventions have been developed to reduce the negative effects of work stress in this environment. OBJECTIVE: This pilot study evaluated the feasibility of a workplace intervention for increasing resilience to stress. The intervention was implemented within the unique constraints characteristic of surgical intensive care units. METHODS: Participants were randomly assigned to an intervention or control group. The mindfulness-based intervention included meditation, mild yoga movement, and music and was conducted in a group format 1 hour a week for 8 weeks in a surgical intensive care unit during work hours. Assessments were performed 1 week before and 1 week after the intervention. RESULTS: The intervention was well received, with a 97% overall retention rate and 100% retention in the intervention group. Work satisfaction, measured with the Utrecht Work Engagement Scale, increased significantly in the intervention group with no change in the control group. Negative correlations were found between the vigor subscale scores of the Utrecht Work Engagement Scale and scores for emotional exhaustion on the Maslach Burnout Inventory and scores for burnout on the Professional Quality of Life scale. Participants rated recognizing their stress response as a main benefit of the intervention. CONCLUSION: Workplace group interventions aimed at decreasing the negative effects of stress can be applied within hospital intensive care units. Despite many constraints, attendance at weekly sessions was high. Institutional support was critical for implementation of this program.

Neuronal networks in mental diseases and neuropathic pain: Beyond brain derived neurotrophic factor and collapsin response mediator proteins.

The brain is a complex network system that has the capacity to support emotion, thought, action, learning and memory, and is characterized by constant activity, constant structural remodeling, and constant attempt to compensate for this remodeling. The basic insight that emerges from complex network organization is that substantively different networks can share common key organizational principles. Moreover, the interdependence of network organization and behavior has been successfully demonstrated for several specific tasks. From this viewpoint, increasing experimental/clinical observations suggest that mental disorders are neural network disorders. On one hand, single psychiatric disorders arise from multiple, multifactorial molecular and cellular structural/functional alterations spreading throughout local/global circuits leading to multifaceted and heterogeneous clinical symptoms. On the other hand, various mental diseases may share functional deficits across the same neural circuit as reflected in the overlap of symptoms throughout clinical diagnoses. An integrated framework including experimental measures and clinical observations will be necessary to formulate a coherent and comprehensive understanding of how neural connectivity mediates and constraints the phenotypic expression of psychiatric disorders.

Prevalence of antipsychotic prescriptions among patients with anxiety disorders treated in inpatient and outpatient psychiatric settings.

BACKGROUND: An increasing number of prescribers are using antipsychotics for treatment of anxiety disorders, despite lack of FDA-approved indications and mixed efficacy results from clinical trials. The objective of this study was to examine the prevalence of antipsychotics prescription in psychiatric inpatients and outpatients with anxiety disorders. METHODS: This is a retrospective study of de-identified data from patients with a DSMIV-TR anxiety disorder diagnosis in an academic psychiatric setting in 2013. The final cohort of patients, after exclusion of bipolar/psychotic comorbidity, includes 1699 patients. Logistic regression models were used to explore associations between antipsychotic prescription and patient characteristics. RESULTS: Among non-psychotic/non-bipolar patients with anxiety disorder, 53.6% of inpatients and 16.6% of outpatients received antipsychotic medication. Rates varied with the disorder. Outpatients with post-traumatic stress disorder (OR: 2.24, 95% CI: 1.66-3.01) and obsessive compulsive disorder (OR: 2.80, 95% CI: 1.86-4.19) received antipsychotic prescriptions more often than those without these diagnoses. Comorbidity with depression was common while comorbidity with borderline personality disorder was rare; both increased odds of receiving prescription of antipsychotics (OR: 1.57, 95% CI: 1.16-2.12 for depression; OR: 2.63, 95% CI 1.42-4.88 for borderline personality disorder, respectively). Additionally, age was significantly associated with increased odds of being on an antipsychotic. Quetiapine and aripripazole were the most prescribed antipsychotics and very few patients received rescue medication for extrapyramidal symptoms. LIMITATIONS: Lack of specific indications for the psychotropic prescriptions. CONCLUSIONS: A substantial percentage of patients with anxiety disorders are prescribed antipsychotics, especially among inpatients. This practice may reflect the severity of the anxiety disorder or the high prevalence of comorbidity. Based on frequency of rescue medication prescription, treatment seemed well tolerated for extra-pyramidal neurological side-effects.

Mindfulness in Motion (MIM): An Onsite Mindfulness Based Intervention (MBI) for Chronically High Stress Work Environments to Increase Resiliency and Work Engagement.

A pragmatic mindfulness intervention to benefit personnel working in chronically high-stress environments, delivered onsite during the workday, is timely and valuable to employee and employer alike. Mindfulness in Motion (MIM) is a Mindfulness Based Intervention (MBI) offered as a modified, less time intensive method (compared to Mindfulness-Based Stress Reduction), delivered onsite, during work, and intends to enable busy working adults to experience the benefits of mindfulness. It teaches mindful awareness principles, rehearses mindfulness as a group, emphasizes the use of gentle yoga stretches, and utilizes relaxing music in the background of both the group sessions and individual mindfulness practice. MIM is delivered in a group format, for 1 hr/week/8 weeks. CDs and a DVD are provided to facilitate individual practice. The yoga movement is emphasized in the protocol to facilitate a quieting of the mind. The music is included for participants to associate the relaxed state experienced in the group session with their individual practice. To determine the intervention feasibility/efficacy we conducted a randomized wait-list control group in Intensive Care Units (ICUs). ICUs represent a high-stress work environment where personnel experience chronic exposure to catastrophic situations as they care for seriously injured/ill patients. Despite high levels of work-related stress, few interventions have been developed and delivered onsite for such environments. The intervention is delivered on site in the ICU, during work hours, with participants receiving time release to attend sessions. The intervention is well received with 97% retention rate. Work engagement and resiliency increase significantly in the intervention group, compared to the wait-list control group, while participant respiration rates decrease significantly pre-post in 6/8 of the weekly sessions. Participants value institutional support, relaxing music, and the instructor as pivotal to program success. This provides evidence that MIM is feasible, well accepted, and can be effectively implemented in a chronically high-stress work environment.

The international Study to Predict Optimized Treatment in Depression (iSPOT-D): outcomes from the acute phase of antidepressant treatment.

We aimed to characterize a large international cohort of outpatients with MDD within a practical trial design, in order to identify clinically useful predictors of outcomes with three common antidepressant medications in acute-phase treatment of major depressive disorder (MDD). The international Study to Predict Optimized Treatment in Depression has presently enrolled 1008 treatment-seeking outpatients (18-65 years old) at 17 sites (five countries). At pre-treatment, we characterized participants by symptoms, clinical history, functional status and comorbidity. Participants were randomized to receive escitalopram, sertraline or venlafaxine-extended release and managed by their physician following usual treatment practices. Symptoms, function, quality of life, and side-effect outcomes were assessed 8 weeks later. The relationship of anxiety to response and remission was assessed by comorbid Axis I diagnosis, presence/absence of anxiety symptoms, and dimensionally by anxiety symptom severity. The sample had moderate-to-severe symptoms, but substantial comorbidity and functional impairment. Of completers at week 8, 62.2% responded and 45.4% reached remission on the 17-item Hamilton Rating Scale for Depression; 53.3% and 37.6%, respectively on the 16-item Quick Inventory of Depressive Symptoms. Functional improvements were seen across all domains. Most participants had side effects that occurred with a frequency of 25% or less and were reported as being in the "none" to minimal/mild range for intensity and burden. Outcomes did not differ across medication groups. More severe anxiety symptoms at pre-treatment were associated with lower remission rates across all medications, independent of depressive severity, diagnostic comorbidity or side effects. Across medications, we found consistent and similar improvements in symptoms and function, and a dimensional prognostic effect of comorbid anxiety symptoms. These equivalent outcomes across treatments lay the foundation for identifying potential neurobiological and genetic predictors of treatment outcome in this sample.

A small randomized pilot study of a workplace mindfulness-based intervention for surgical intensive care unit personnel: effects on salivary α-amylase levels.

OBJECTIVE: To determine whether a workplace stress-reduction intervention decreases reactivity to stress among personnel exposed to a highly stressful occupational environment. METHODS: Personnel from a surgical intensive care unit were randomized to a stress-reduction intervention or a waitlist control group. The 8-week group mindfulness-based intervention included mindfulness, gentle yoga, and music. Psychological and biological markers of stress were measured 1 week before and 1 week after the intervention. RESULTS: Levels of salivary α-amylase, an index of sympathetic activation, were significantly decreased between the first and second assessments in the intervention group with no changes in the control group. There was a positive correlation between salivary α-amylase levels and burnout scores. CONCLUSIONS: These data suggest that this type of intervention could decrease not only reactivity to stress but also the risk of burnout.

GM1 ganglioside enhances Ret signaling in striatum.

It has been proposed that GM1 ganglioside promotes neuronal growth, phenotypic expression, and survival by modulating tyrosine kinase receptors for neurotrophic factors. Our studies tested the hypothesis that GM1 exerts its neurotrophic action on dopaminergic neurons, in part, by interacting with the GDNF (glia cell-derived neurotrophic factor) receptor complex, Ret tyrosine kinase and GFRα1 co-receptor. GM1 addition to striatal slices in situ increased Ret activity in a concentration- and time-dependent manner. GM1-induced Ret activation required the whole GM1 molecule and was inhibited by the kinase inhibitors PP2 and PP1. Ret activation was followed by Tyr1062 phosphorylation and PI3 kinase/Akt recruitment. The Src kinase was associated with Ret and GM1 enhanced its phosphorylation. GM1 responses required the presence of GFRα1, and there was a GM1 concentration-dependent increase in the binding of endogenous GDNF which paralleled that of Ret activation. Neutralization of the released GDNF did not influence the Ret response to GM1, and GM1 had no effect on GDNF release. Our in situ studies suggest that GM1 via GFRα1 modulates Ret activation and phosphorylation in the striatum and provide a putative mechanism for its effects on dopaminergic neurons. Indeed, chronic GM1 treatment enhanced Ret activity and phosphorylation in the striatum of the MPTP-mouse and kinase activation was associated with recovery of dopamine and DOPAC deficits. It has been proposed that the ganglioside GM1 promotes neuronal growth, phenotypic expression, and survival by modulating tyrosine kinase receptors for neurotrophic factors. We provide evidence that the GM1 enhances the activity of Ret tyrosine kinase receptor for glia cell-derived neurotrophic factor (GDNF) in the striatum in situ and in vivo, and propose that this might be a mechanism for GM1's neurotrophic actions on dopaminergic neurons. Ret activation is followed by Tyr1062 and Tyr981 phosphorylation and recruitment of PI3-K/Akt, Erk, and Src signaling. GM1 apparently acts by increasing the binding of endogenous GDNF to GFRα1 co-receptor, which is required for the GM1 effect on Ret.

Mapping CRMP3 domains involved in dendrite morphogenesis and voltage-gated calcium channel regulation.

Although hippocampal neurons are well-distinguished by the morphological characteristics of their dendrites and their structural plasticity, the mechanisms involved in regulating their neurite initiation, dendrite growth, network formation and remodeling are still largely unknown, in part because the key molecules involved remain elusive. Identifying new dendrite-active cues could uncover unknown molecular mechanisms that would add significant understanding to the field and possibly lead to the development of novel neuroprotective therapy because these neurons are impaired in many neuropsychiatric disorders. In our previous studies, we deleted the gene encoding CRMP3 in mice and identified the protein as a new endogenous signaling molecule that shapes diverse features of the hippocampal pyramidal dendrites without affecting axon morphology. We also found that CRMP3 protects dendrites against dystrophy induced by prion peptide PrP(106-126). Here, we report that CRMP3 has a profound influence on neurite initiation and dendrite growth of hippocampal neurons in vitro. Our deletional mapping revealed that the C-terminus of CRMP3 probably harbors its dendritogenic capacity and supports an active transport mechanism. By contrast, overexpression of the C-terminal truncated CRMP3 phenocopied the effect of CRMP3 gene deletion with inhibition of neurite initiation or decrease in dendrite complexity, depending on the stage of cell development. In addition, this mutant inhibited the activity of CRMP3, in a similar manner to siRNA. Voltage-gated calcium channel inhibitors prevented CRMP3-induced dendritic growth and somatic Ca(2+) influx in CRMP3-overexpressing neurons was augmented largely via L-type channels. These results support a link between CRMP3-mediated Ca(2+) influx and CRMP3-mediated dendritic growth in hippocampal neurons.

Shared decision making and other variables as correlates of satisfaction with health care decisions in a United States national survey.

OBJECTIVE: The purpose of this study was to examine the relationship between shared decision-making (SDM) and satisfaction with decision (SWD) within a larger survey of patient decision-making in health care consultations. METHODS: A randomly selected age-proportionate national sample of adults (aged 21-70 years) stratified on race, ethnicity, and gender (N=488) was recruited from a health research volunteer registry and completed an online survey with reference to a recent health consultation. Measures included the shared decision making-9 questionnaire (SDM-Q-9), Satisfaction With Decision (SWD) scale, sociodemographic, health, and other standardized decision-making measures. Forward selection weighted multiple regression analysis was used to model correlates of SWD. RESULTS: After controlling for sociodemographic variables, SDM-Q-9 total score was associated with SWD, adjusted R(2)=.368, p<.001. Three of nine SDM-Q-9 items accounted for significant proportions of variance in SWD. CONCLUSION: SDM was positively associated with SWD and was strongest for three areas of SDM: patients being helped in a health care consultation with understanding information, with treatment preference elicitation, and with weighing options thoroughly. PRACTICE IMPLICATIONS: By identifying variables such as SDM that are associated with SWD, health care interventions can better target modifiable factors to enhance satisfaction and other outcomes.