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Alzheimer's disease (AD) biomarkers and stroke risk factors independently predict cognitive impairment, likely through independent disease pathways. However, limited work has sought to describe the dynamic interplay between these important risk factors. This article evaluated the interaction between stroke risk and AD biomarkers on hippocampal volume and cognitive performance. We first evaluated the interaction between stroke risk factors and AD biomarkers using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI, n = 1202). We then extended our findings to an independent autopsy data set from the National Alzheimer's Coordinating Center (NACC, n = 1122) using measures of AD pathology. Stroke risk was quantified using the Framingham Stroke Risk Profile. In ADNI, stroke risk interacted with tau and amyloid levels in relation to baseline and longitudinal cognitive performance. Similarly, in NACC, stroke risk interacted with amyloid and tau positivity on cognitive performance. The effect of stroke risk factors on cognition was strongest in the absence of AD biomarkers or neuropathology, providing additional evidence that AD biomarkers and stroke risk factors relate to cognition through independent pathways.
Copyright © 2015 Elsevier Inc. All rights reserved.
BACKGROUND - Schizotypy is a range of perceptual experiences and personality features related to risk and familial predisposition to psychosis. Despite evidence that schizotypy is related to psychosis vulnerability, very little is known about the expression of schizotypal traits in individuals with a psychotic disorder, and their relationship to clinical symptoms, cognition, and psychosocial functioning.
METHODS - 59 healthy subjects and 68 patients with a psychotic disorder (47 schizophrenia spectrum disorder; 21 bipolar disorder with psychotic features) completed four schizotypy scales, the Perceptual Aberration Scale, the Revised Physical and Social Anhedonia Scales, and the Schizotypal Personality Questionnaire, a brief neuropsychological assessment, and a self-report measure of quality of life. Clinical symptoms of psychosis were quantified in patients with the Positive and Negative Syndrome Scale (PANSS).
RESULTS - Psychosis patients scored higher than healthy subjects on all schizotypy scales. Correlations between schizotypy and PANSS scores were modest, ranging from r=.06 to r=.43, indicating that less than 20% of the variance in self-reported schizotypy overlapped with clinical symptoms. After controlling for clinical symptoms, patients with schizophrenia spectrum disorders reported higher levels of cognitive-perceptual disturbances and negative traits than patients with bipolar disorder. Elevated schizotypy was associated with lower cognitive functioning and self-reported quality of life.
CONCLUSIONS - Schizotypal personality traits are markedly elevated in psychotic disorders, especially schizophrenia spectrum disorders, relatively weakly correlated with positive and negative psychotic symptoms, and associated with greater cognitive impairment and lower quality of life. Assessing schizotypy in patients with psychosis may be useful for predicting functional outcome and differential diagnosis.
Copyright © 2015 Elsevier B.V. All rights reserved.
BACKGROUND - Social impairments are a hallmark feature of schizophrenia and are a key predictor of functional disability. Deficits in social information processing likely underlie social impairment; however, this relationship is understudied. We previously demonstrated that patients with schizophrenia fail to habituate to neutral faces, providing evidence for an alteration in basic social information processing. It remains unknown whether patients with schizophrenia also show deficits in processing of more complex social information. Out-group bias provides an excellent opportunity to test complex social information processing because the bias requires basic face processing skills, the ability to discriminate between groups, as well as the ability to categorize oneself into a salient social group.
METHODS - Study participants were 23 patients with schizophrenia and 21 controls. Using functional magnetic resonance imaging, habituation of response to 120 s of repeated presentations of faces was assessed in participants who viewed either same-gender faces or opposite-gender faces. The interaction between face gender (same/opposite) and group was examined in three key regions: amygdala, hippocampus, and visual cortex. Social impairment was measured using the PANSS and correlations between social impairment and out-group effect (main effect of face type) were performed in patients.
RESULTS - Patients with schizophrenia had aberrant neural responses to opposite-gender faces (interaction, p<.05 corrected). Healthy controls showed an immediate heightened response to opposite-gender faces relative to same-gender faces; but in patients this effect was substantially delayed (~70s). In patients with schizophrenia, the out-group bias was significantly correlated with social impairment. Patients with no social impairment showed a heightened neural response to opposite-gender faces after 30s, whereas patients with mild-moderate social impairment failed to ever show a heightened response.
CONCLUSION - Alterations in neural responses during out-group processing predicted degree of social impairment in patients with schizophrenia; thus, neural responses to opposite-gender faces may provide a novel measure for studies of treatment response and disease outcome.
Copyright © 2015 Elsevier B.V. All rights reserved.
BACKGROUND - The classification of catatonia has fluctuated and underwent recent changes in DSM-5. The current study examines the prevalence of catatonia signs, estimates the utility of diagnostic features, identifies core catatonia signs, and explores their underlying structure.
METHOD - We screened 339 acutely ill medical and psychiatric patients with the Bush Francis Catatonia Rating Scale (BFCRS). We examined prevalence and severity of catatonia signs and compared BFCRS, DSM-IV and DSM-5 diagnoses. We used principal component analysis (PCA) to examine the factorial validity of catatonia and item response theory (IRT) to estimate each sign's utility and reliability.
RESULTS - Out of the 339 patients, 300 were diagnosed with catatonia using the BFCRS and 232 catatonia diagnoses were validated by the treating provider based on selection for treatment with benzodiazepines or electroconvulsive therapy. Of the 232 validated catatonia cases, 211 (91%) met DSM-IV criteria but only 170 (73%) met DSM-5 criteria for catatonia. Staring was the most prevalent catatonia sign. PCA identified three components, interpretable as "Increased, Abnormal and Decreased Psychomotor Activity," although 63% of the variance was unexplained. IRT showed that Excitement, Waxy Flexibility and Immobility/Stupor were the best indicators of each factor. The BFCRS had many redundant items and as a whole had low reliability at low severity of catatonia, but good reliability at moderate-high severity of catatonia.
CONCLUSIONS - The structure of catatonia remains to be discovered.
Published by Elsevier B.V.
BACKGROUND - A cognitive concern from the patient, informant, or clinician is required for the diagnosis of mild cognitive impairment (MCI); however, the cognitive and neuroanatomical correlates of complaint are poorly understood.
OBJECTIVE - We assessed how self-complaint relates to cognitive and neuroimaging measures in older adults with MCI.
METHOD - MCI participants were drawn from the Alzheimer's Disease Neuroimaging Initiative and dichotomized into two groups based on the presence of self-reported memory complaint (no complaint n = 191, 77 ± 7 years; complaint n = 206, 73 ± 8 years). Cognitive outcomes included episodic memory, executive functioning, information processing speed, and language. Imaging outcomes included regional lobar volumes (frontal, parietal, temporal, cingulate) and specific medial temporal lobe structures (hippocampal volume, entorhinal cortex thickness, parahippocampal gyrus thickness).
RESULTS - Linear regressions, adjusting for age, gender, race, education, Mini-Mental State Examination score, mood, and apolipoprotein E4 status, found that cognitive complaint related to immediate (β = -1.07, p < 0.001) and delayed episodic memory performances assessed on a serial list learning task (β = -1.06, p = 0.001) but no other cognitive measures or neuroimaging markers.
CONCLUSIONS - Self-reported memory concern was unrelated to structural neuroimaging markers of atrophy and measures of information processing speed, executive functioning, or language. In contrast, subjective memory complaint related to objective verbal episodic learning performance. Future research is warranted to better understand the relation between cognitive complaint and surrogate markers of abnormal brain aging, including Alzheimer's disease, across the cognitive aging spectrum.
INTRODUCTION - Recent research suggests a relationship of inflammatory bowel disease (IBD) and depression. Our objective was to evaluate for improvement of depressive symptoms with treatment of IBD using immunosuppressive medications.
METHODS - A retrospective study of consecutive patients with IBD started on immunosuppressive agents [anti-tumor necrosis factor (anti-TNF) or immunomodulator therapy] was conducted. Patients were evaluated if disease activity indices using Harvey Bradshaw Index for Crohn's disease (CD) and Simple Clinical Colitis Disease Activity Index for ulcerative colitis (UC) and depressive indices using Patient Health Questionnaire-9 (PHQ-9) scores were obtained before and at least 30 days after initiation of therapy.
RESULTS - Sixteen patients with UC and 53 patients with CD (all with active disease symptoms) were evaluated over a 60 day median follow-up evaluation (range 30, 140 days). Twenty-two patients started on immunomodulator therapy, and 47 patients started on anti-TNF therapy. Crohn's disease patients had significantly decreased PHQ-9 scores at follow-up [median 9 (range 3, 14) to 4 (1, 8)], with significant decreases only in those started on anti-TNF therapy. Changes in PHQ-9 and CRP were correlated (ρ = 0.38, p < 0.05). In patients with UC, PHQ-9 scores [5 (3, 9) to 2 (0, 5)] were significantly decreased. Percentage at risk of moderate to severe depression (PHQ-9 scores ≥10) was lower after treatment [Crohn's disease 51-18 % (p < 0.05), ulcerative colitis 18-0 %].
CONCLUSION - Depressive scores decreased significantly in patients with IBD treated with immunosuppressive therapy and the number at risk for moderate to severe depression improved significantly.
OBJECTIVES - To determine whether delirium during the hospital stay predicted health-related quality of life (HRQOL) at 1 year after injury in trauma intensive care unit (ICU) survivors without intracranial hemorrhage, and to examine the association between depressive and posttraumatic stress disorder (PTSD) symptoms and each of the HRQOL domains at 1-year follow-up.
DESIGN - Prognostic cohort with a 1-year follow-up.
SETTING - Level 1 trauma ICU.
PARTICIPANTS - Adult patients without intracranial hemorrhage (N=173) admitted to a level 1 trauma ICU.
INTERVENTIONS - Not applicable.
MAIN OUTCOME MEASURES - HRQOL was measured with the Medical Outcomes Study 36-Item Short-Form Health Survey at 1 year after traumatic injury.
RESULTS - Average delirium duration ± SD was .51±1.1 days. Hierarchical multivariable linear regression analyses did not find a statistical relationship between delirium and HRQOL at 1-year follow-up. However, increased levels of depressive symptoms at 1 year were statistically associated with poorer functioning in all physical and mental health HRQOL domains, whereas PTSD at 1 year was statistically associated with all HRQOL domains except role-physical (P<.05).
CONCLUSIONS - There was no statistical association between delirium during the hospital stay and HRQOL at 1 year, which may be due to the short time spent in delirium by our study population. Depressive symptoms demonstrated a stronger relationship with mental and physical HRQOL domains at 1 year than PTSD, indicating their own unique pathway after trauma. Findings lend support for the separate assessment and management of depression and PTSD. Additional research on the duration and subtypes of delirium is needed within the trauma ICU population, as the effects are not widely known.
Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
OBJECTIVE - Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a combined genome-wide association study (GWAS) of Tourette's syndrome and OCD.
METHOD - The authors conducted a GWAS in 2,723 cases (1,310 with OCD, 834 with Tourette's syndrome, 579 with OCD plus Tourette's syndrome/chronic tics), 5,667 ancestry-matched controls, and 290 OCD parent-child trios. GWAS summary statistics were examined for enrichment of functional variants associated with gene expression levels in brain regions. Polygenic score analyses were conducted to investigate the genetic architecture within and across the two disorders.
RESULTS - Although no individual single-nucleotide polymorphisms (SNPs) achieved genome-wide significance, the GWAS signals were enriched for SNPs strongly associated with variations in brain gene expression levels (expression quantitative loci, or eQTLs), suggesting the presence of true functional variants that contribute to risk of these disorders. Polygenic score analyses identified a significant polygenic component for OCD (p=2×10(-4)), predicting 3.2% of the phenotypic variance in an independent data set. In contrast, Tourette's syndrome had a smaller, nonsignificant polygenic component, predicting only 0.6% of the phenotypic variance (p=0.06). No significant polygenic signal was detected across the two disorders, although the sample is likely underpowered to detect a modest shared signal. Furthermore, the OCD polygenic signal was significantly attenuated when cases with both OCD and co-occurring Tourette's syndrome/chronic tics were included in the analysis (p=0.01).
CONCLUSIONS - Previous work has shown that Tourette's syndrome and OCD have some degree of shared genetic variation. However, the data from this study suggest that there are also distinct components to the genetic architectures of these two disorders. Furthermore, OCD with co-occurring Tourette's syndrome/chronic tics may have different underlying genetic susceptibility compared with OCD alone.
Social impairment is a core feature of schizophrenia, present from the pre-morbid stage and predictive of outcome, but the etiology of this deficit remains poorly understood. Successful and adaptive social interactions depend on one's ability to make rapid and accurate judgments about others in real time. Our surprising ability to form accurate first impressions from brief exposures, known as "thin slices" of behavior has been studied very extensively in healthy participants. We sought to examine affect and social trait judgment from thin slices of static or video stimuli in order to investigate the ability of schizophrenic individuals to form reliable social impressions of others. 21 individuals with schizophrenia (SZ) and 20 matched healthy participants (HC) were asked to identify emotions and social traits for actors in standardized face stimuli as well as brief video clips. Sound was removed from videos to remove all verbal cues. Clinical symptoms in SZ and delusional ideation in both groups were measured. Results showed a general impairment in affect recognition for both types of stimuli in SZ. However, the two groups did not differ in the judgments of trustworthiness, approachability, attractiveness, and intelligence. Interestingly, in SZ, the severity of positive symptoms was correlated with higher ratings of attractiveness, trustworthiness, and approachability. Finally, increased delusional ideation in SZ was associated with a tendency to rate others as more trustworthy, while the opposite was true for HC. These findings suggest that complex social judgments in SZ are affected by symptomatology.
Copyright © 2014 Elsevier B.V. All rights reserved.
OBJECTIVES - In the emergency department (ED), health care providers miss delirium approximately 75% of the time, because they do not routinely screen for this syndrome. The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) is a brief (<1 minute) delirium assessment that may be feasible for use in the ED. The study objective was to determine its validity and reliability in older ED patients.
METHODS - In this prospective observational cohort study, patients aged 65 years or older were enrolled at an academic, tertiary care ED from July 2009 to February 2012. An emergency physician (EP) and research assistants (RAs) performed the CAM-ICU. The reference standard for delirium was a comprehensive (~30 minutes) psychiatrist assessment using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. All assessments were blinded to each other and were conducted within 3 hours. Sensitivities, specificities, and likelihood ratios were calculated for both the EP and the RAs using the psychiatrist's assessment as the reference standard. Kappa values between the EP and RAs were also calculated to measure reliability.
RESULTS - Of 406 patients enrolled, 50 (12.3%) had delirium. The median age was 73.5 years old (interquartile range [IQR] = 69 to 80 years), 202 (49.8%) were female, and 57 (14.0%) were nonwhite. The CAM-ICU's sensitivities were 72.0% (95% confidence interval [CI] = 58.3% to 82.5%) and 68.0% (95% CI = 54.2% to 79.2%) in the EP and RAs, respectively. The CAM-ICU's specificity was 98.6% (95% CI = 96.8% to 99.4%) for both raters. The negative likelihood ratios (LR-) were 0.28 (95% CI = 0.18 to 0.44) and 0.32 (95% CI = 0.22 to 0.49) in the EP and RAs, respectively. The positive likelihood ratios (LR+) were 51.3 (95% CI = 21.1 to 124.5) and 48.4 (95% CI = 19.9 to 118.0), respectively. The kappa between the EP and RAs was 0.92 (95% CI = 0.85 to 0.98), indicating excellent interobserver reliability.
CONCLUSIONS - In older ED patients, the CAM-ICU is highly specific, and a positive test is nearly diagnostic for delirium when used by both the EP and RAs. However, the CAM-ICU's sensitivity was modest, and a negative test decreased the likelihood of delirium by a small amount. The consequences of a false-negative CAM-ICU are unknown and deserve further study.
© 2014 by the Society for Academic Emergency Medicine.