Introduction of a Novel Ethics Curriculum to the Third-Year Psychiatry Clerkship Experience.

OBJECTIVE: The purpose of this study was to determine if a brief ethics curriculum embedded in a third-year required clerkship differentially impacted students' self-rated confidence versus competence (determined by a written examination) regarding ethical principles related to psychiatry. METHODS: Using a naturalistic design, 270 medical students at the University of Washington were assigned to one of three groups during their third-year psychiatry clerkship: a control group with no additional ethics content, a group with access to a pre-recorded video ethics curriculum, or a group with live didactic sessions in addition to the video curriculum. All students took a pre- and post-test that assessed their confidence and competence in ethical theory and behavioral health ethics. RESULTS: Confidence and competence were not statistically different across the three groups prior to completing the curriculum (p > 0.1). Post-test scores on confidence in behavioral health ethics were not significantly different between the three groups (p > 0.05). Post-test scores on confidence in ethical theory were significantly higher in the video-only and video + discussion group as compared to the control group (3.74 ± 0.55 and 4.00 ± 0.44 vs. 3.19 ± 0.59 respectively; p < 0.0001). Both the video-only and video + discussion group showed greater improvement in competence in ethical theory and application than the control group (0.68 ± 0.30 and 0.76 ± 0.23 vs. 0.31 ± 0.33, respectively; p < 0.0001) and behavioral health ethics (0.79 ± 0.14 and 0.85 ± 0.14 vs. 0.59 ± 0.15, respectively; p < 0.002). CONCLUSIONS: With the addition of this ethics curriculum, students showed both increased confidence and competence in their ability to analyze ethical situations as well as increased competence regarding behavioral health ethics.

Elements of an Excellent Psychiatry Clerkship Experience: A Survey Study of Graduating Medical Students.

OBJECTIVE: One possible factor associated with choosing psychiatry as a career is students rating their psychiatry clerkship as excellent. Although this suggests that an excellent clerkship may improve recruitment into psychiatry, to our knowledge there has never been a multi-site survey study of graduating medical students that identify what factors lead to an excellent clerkship rating. The purpose of this study was to determine factors that medical student find important for an excellent psychiatry clerkship experience. METHODS: A total of 1457 graduating medical students at eight institutions were sent a 22-item Likert-type survey about what clinical and administrative factors they considered when rating their psychiatry clerkship via email in the fall of their last year. 357 (24.5%) responded and Z-test, t-tests, and multiple regression analyses were carried out. RESULTS: The factors which students rated higher than the mean included planned application to psychiatry residency, clear expectations, a transparent grading process, feeling part of a team, timely feedback by faculty, and a competent clerkship coordinator and director. Lectures, active learning, and self-study were rated as less pertinent, and the overall clerkship rating did differ between students going into psychiatry versus other specialties. CONCLUSIONS: Although the low response undermines the validity of findings, by improving the administration of the clerkship with clear expectations, grading, feedback, and by encouraging clinical teams to fully integrate students clerkship ratings might improve which could potentially improve recruitment. Future research could further quantify and qualify these parameters and compare psychiatric clerkships to other clerkships.

Lethal Means Assessment in Psychiatric Emergency Services: Frequency and Characteristics of Assessment.

OBJECTIVE: Lethal means safety is an effective suicide prevention strategy with demonstrated results at the population level, yet individual-level uptake is less well understood. METHODS: Using automated data extraction methods, we conducted an investigation of electronic health records from psychiatric emergency service (PES) patients from January 1, 2012 to December 31, 2017 at a busy urban medical center in the Pacific Northwest. At each PES mental health evaluation, every patient received a Suicide Risk Assessment during which providers used an electronic template with standardized fields to record lethal means access and other suicide risk factors. RESULTS: We assessed 32,658 records belonging to 15,652 patients. Among all visits, 69.9% (n = 22,824) had some documentation of lethal means assessment. However, 54.1% (n = 17,674) of all visits lacked some or all potential documentation detail. Additionally, among 59.6% of visits in which a patient had documented access to lethal means, the specific means available were not indicated. Across the twenty risk and demographic factors we assessed, the prevalence of documentation did not vary by any given risk factor and only varied minimally by age and race. For example, when comparing visits which indicated family history of suicide to those which indicated no family history of suicide, the prevalence ratio was 0.99 (95% CI: 0.95, 1.03). CONCLUSION: Despite the high-risk patient population, mental health focus of the facility, and the presence of a standardized tool, lethal means documentation was suboptimal. In alignment with recent recommendations, our findings indicate that additional focus on implementation is needed to improve documentation of lethal means assessment.HighlightsFifteen times larger than prior comparable studiesFindings demonstrate persistent under-documentation patterns in new setting and regionStandardized methods likely needed to improve documentation detail and frequency.

Changes in neuronal activation patterns in response to androgen deprivation therapy: a pilot study.

BACKGROUND: A common treatment option for men with prostate cancer is androgen deprivation therapy (ADT). However, men undergoing ADT may experience physical side effects, changes in quality of life and sometimes psychiatric and cognitive side effects. METHODS: In this study, hormone naïve patients without evidence of metastases with a rising PSA were treated with nine months of ADT. Functional magnetic resonance imaging (fMRI) of the brain during three visuospatial tasks was performed at baseline prior to treatment and after nine months of ADT in five subjects. Seven healthy control patients, underwent neuroimaging at the same time intervals. RESULTS: ADT patients showed reduced, task-related BOLD-fMRI activation during treatment that was not observed in control subjects. Reduction in activation in right parietal-occipital regions from baseline was observed during recall of the spatial location of objects and mental rotation. CONCLUSIONS: Findings, while preliminary, suggest that ADT reduces task-related neural activation in brain regions that are involved in mental rotation and accurate recall of spatial information.

Network Optimization of Functional Connectivity Within Default Mode Network Regions to Detect Cognitive Decline.

The rapid aging of the world's population is causing an increase in the prevalence of cognitive decline and degenerative brain disease in the elderly. Current diagnoses of amnestic and nonamnestic mild cognitive impairment, which may represent early stage Alzheimer's disease or related degenerative conditions, are based on clinical grounds. The recent emergence of advanced network analyses of functional magnetic resonance imaging (fMRI) data taken at cognitive rest has provided insight that declining functional connectivity of the default mode network (DMN) may be correlated with neurological disorders, and particularly prodromal Alzheimer's disease. The goal of this paper is to develop a network analysis technique using fMRI data to characterize transition stages from healthy brain aging to cognitive decline. Previous studies primarily focused on inter-nodal connectivity of the DMN and often assume functional homogeneity within each DMN region. In this paper, we develop a technique that focuses on identifying critical intra-nodal DMN connectivity by incorporating sparsity into connectivity modeling of the k -cardinality tree (KCT) problem. Most biological networks are efficient and formed by sparse connections, and the KCT can potentially reveal sparse connectivity patterns that are biologically informative. The KCT problem is NP-hard, and existing solution approaches are mostly heuristic. Mathematical formulations of the KCT problem in the literature are not compact and do not provide good solution bounds. This paper presents new KCT formulations and a fast heuristic approach to efficiently solve the KCT models for large DMN regions. The results in this paper demonstrate that traditional fMRI group analysis on DMN regions cannot detect any statistically significant connectivity differences between normal aging and cognitively impaired subjects in DMN regions, and the proposed KCT approaches are more sensitive than the state-of-the-art regional homogeneity approach in detecting significant differences in both left and right medial temporal regions of the DMN.

Migration from a mitogenic niche promotes cell-cycle exit.

During development, neural precursors proliferate in one location and migrate to the residence of their mature function. The transition from a proliferative stage to a migratory stage is a critical juncture; errors in this process may result in tumor formation, mental retardation, or epilepsy. This transition could be the result of a simple sequential process in which precursors exit the cell cycle and then begin to migrate or a dynamically regulated process in which migration away from a mitogenic niche induces precursors to exit the cell cycle. Here, we show, using in vivo and in vitro approaches, that granule cell precursors proliferate when they are exposed to the microenvironment of the external granule cell layer (EGL) and exit the cell cycle as a result of migrating away from this environment. In vivo, granule cell precursors that remain in the EGL because of impaired migration continue to proliferate in the mitogenic niche of the EGL. In vitro, granule cell precursors that are introduced into an organotypic cerebellar slice proliferate preferentially in the EGL. We identify Sonic Hedgehog as a critical component of the EGL mitogenic niche. Together, these data indicate that migration away from a mitogenic niche promotes transition from a proliferative to a nonproliferative, migratory stage.

The association between higher order abilities, processing speed, and age are variably mediated by white matter integrity during typical aging.

Although aging is associated with changes in brain structure and cognition it remains unclear which specific structural changes mediate individual cognitive changes. Several studies have reported that white matter (WM) integrity, as assessed by diffusion tensor imaging (DTI), mediates, in part, age-related differences in processing speed (PS). There is less evidence for WM integrity mediating age-related differences in higher order abilities (e.g., memory and executive functions). In 165 typically aging adults (age range 54-89) we show that WM integrity in select cerebral regions is associated with higher cognitive abilities and accounts variance not accounted for by PS or age. Specifically, voxel-wise analyses using tract-based spatial statistics (TBSS) revealed that WM integrity was associated with reasoning, cognitive flexibility and PS, but not memory or word fluency, after accounting for age and gender. While cerebral fractional anisotropy (FA) was only associated with PS; mean (MD), axial (AD) and radial (RD) diffusivity were associated with reasoning and flexibility. Reasoning was selectively associated with left prefrontal AD, while cognitive flexibility was associated with MD, AD and RD throughout the cerebrum. Average WM metrics within select WM regions of interest accounted for 18% and 29% of the variance in reasoning and flexibility, respectively, similar to the amount of variance accounted for by age. WM metrics mediated ~50% of the age-related variance in reasoning and flexibility and different proportions, 11% for reasoning and 44% for flexibility, of the variance accounted for by PS. In sum, (i) WM integrity is significantly, but variably, related to specific higher cognitive abilities and can account for a similar proportion of variance as age, and (ii) while FA is selectively associated with PS; while MD, AD and RD are associated with reasoning, flexibility and PS. This illustrates both the anatomical and cognitive selectivity of structure-cognition relationships in the aging brain.

Midlife memory improvement predicts preservation of hippocampal volume in old age.

This study examines whether midlife change in episodic memory predicts hippocampal volume in old age. From the Seattle Longitudinal Study we retrospectively identified 84 healthy, cognitively normal individuals, age 52 to 87, whose episodic memory had reliably declined (n = 33), improved (n = 28) or remained stable (n = 23) over a 14-year period in midlife (age 43-63). Midlife memory improvement was associated with 13% larger hippocampal volume (p < 0.01) in old age (age 66-87), compared with old age individuals whose midlife episodic memory had either declined or remained stable during midlife. Midlife memory change did not predict total hippocampal volume for those currently in late middle age (age 52-65). The pattern of findings was not modified by gender, apolipoprotein ε4 status, education or current memory performance. Change in midlife memory scores over 14 years, but not any single assessment, predicted hippocampal volumes in old age, emphasizing the importance of longitudinal data in examining brain-cognition relationships. These findings suggest that improvement in memory in midlife is associated with sparing of hippocampal volume in later life.

Neuroimaging in the clinical diagnosis of dementia: observations from a memory disorders clinic.

OBJECTIVES: To determine how often neuroimaging confirms, clarifies, or contradicts initial diagnoses of late-life cognitive disorders. DESIGN: Retrospective case review. SETTING: Outpatient clinic specializing in memory disorders. PARTICIPANTS: One hundred ninety-three consecutively referred cognitively impaired patients. MEASUREMENTS: Diagnoses using research criteria were developed for each patient at the first visit and ranged from cognitive impairment without dementia to dementias of single, complex, or indeterminate etiology. Structural (noncontrast magnetic resonance imaging) and perfusion (technetium-99m ethyl cysteine dimer single photon emission computed tomography) images were categorized together as normal, suggestive of specific diseases, or abnormal/not diagnostic. RESULTS: When a single neurodegenerative disease was suspected clinically (n=94), imaging confirmed the diagnosis in 50, contradicted the diagnosis in 32, and was abnormal/not diagnostic in 12. When more than one neurodegenerative etiology was clinically suspected (n=21), imaging assigned a single diagnosis in 13 and only cerebrovascular disease in one and was abnormal/not diagnostic in seven. In dementia not otherwise specified (NOS) (n=33), imaging suggested a specific etiology in 23 and was abnormal/not diagnostic in 10. Abnormal/not diagnostic images were more common in cognitive disorder NOS (n=25, 68%) than in other clinical groups (22%, chi-square=22.8 P<.001). Neuroimaging indicators of cerebrovascular disease were common (60% prevalence) but not predicted by the presence of vascular risk factors alone. CONCLUSION: Overall, neuroimaging confirmed, clarified, or contradicted the initial clinical diagnosis in more than 80% of patients, whereas fewer than 20% had abnormal/not diagnostic patterns. Imaging suggested a complex dementia etiology in 21% of cases clinically thought to be caused by a single process, whereas 46% of complex clinical differential diagnoses appeared to reflect a single causal pattern. Further work is needed to determine whether refinement of clinical diagnoses using specialized neuroimaging improves clinical decision-making and patient outcomes.

Neural activation patterns during working memory tasks and OSA disease severity: preliminary findings.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with cognitive impairments in working memory (WM). Neuronal activation during WM tasks can be indirectly assessed by blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI). The purpose of this study was to describe BOLD-fMRI responses during 2 separate working memory tasks and a finger tapping task in men with OSA. A secondary aim was to explore the possible relation between OSA severity (apnea/hypopnea index) and BOLD-fMRI signal patterns. METHODS: Nine treatment-naïve men (mean age [+/- SD] of 45.7 [+/- 6.6] years) with OSA underwent BOLD fMRI testing on a research-dedicated university-based MRI scanner. During BOLD-fMRI subjects performed a Paced Auditory Serial Addition task (PASAT), an auditory N-Back task (2-BACK) task, and an alternating finger tapping. RESULTS: PASAT and 2-BACK tasks produced similar patterns of increased bilateral activation in posterior parietal, prefrontal and cerebellar regions. BOLD signal deactivations were observed within posterior cingulate, retrosplenial and inferior frontal regions during PASAT and 2-BACK, but not during tapping. With increased disease severity, BOLD activation patterns were increased in the right parietal lobe, but decreased in the cerebellar vermis. CONCLUSIONS: These preliminary findings suggest that the severity of OSA may correlate with neural activation during tasks of working memory, potentially reflecting compensatory neural responses in severe disease.

Altered medial temporal lobe responses during visuospatial encoding in healthy APOE*4 carriers.

The apolipoprotein varepsilon4 allele (APOE*4) is a major genetic risk factor for Alzheimer's disease (AD) and has been associated with altered cortical activation as assessed by functional neuroimaging in cognitively normal younger and older carriers. We chose to evaluate medial temporal lobe (MTL) activation during encoding and recognition using a perspective-dependent (route or survey) visuospatial memory task by monitoring the blood-oxygen-level-dependent (BOLD) fMRI response in older, non-demented APOE*4 carriers (APOE*4+) and non-carriers (APOE*4-). During encoding, the APOE*4- group had greater average task-associated BOLD responses in ventral visual pathways, including the MTLs, as compared to the APOE*4+ group. Furthermore, MTL activation was greater during route encoding than survey encoding on average in APOE*4-, but not APOE*4+, subjects. During recognition, both groups performed similarly and no BOLD signal differences were found. Finally, within-group analysis revealed MTL activation during encoding was correlated with recognition performance in APOE*4-, but not APOE*4+ subjects. Reduced task-associated MTL activation that does not correlate with either visuospatial perspective or task performance suggests that MTL dysregulation occurs prior to clinical symptoms of dementia in APOE*4 carriers.

BDNF stimulates migration of cerebellar granule cells.

During development of the nervous system, neural progenitors arise in proliferative zones, then exit the cell cycle and migrate away from these zones. Here we show that migration of cerebellar granule cells out of their proliferative zone, the external granule cell layer (EGL), is impaired in Bdnf(-/-) mice. The reason for impaired migration is that BDNF directly and acutely stimulates granule cell migration. Purified Bdnf(-/-) granule cells show defects in initiation of migration along glial fibers and in Boyden chamber assays. This phenotype can be rescued by exogenous BDNF. Using time-lapse video microscopy we find that BDNF is acutely motogenic as it stimulates migration of individual granule cells immediately after addition. The stimulation of migration reflects both a chemokinetic and chemotactic effect of BDNF. Collectively, these data demonstrate that BDNF is directly motogenic for granule cells and provides a directional cue promoting migration from the EGL to the internal granule cell layer (IGL).