JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Meta-Analysis of Anti-Toxoplasma gondii IgM Antibodies in Acute Psychosis.
Schizophr Bull
PUBLISHED: 11-12-2014
Show Abstract
Hide Abstract
A number of different infections are associated with acute psychosis. However, relationships between infections and acute psychosis in patients with schizophrenia have not been extensively explored. Exposure to Toxoplasma gondii is a replicated risk factor for schizophrenia. Previous studies have focused on T. gondii IgG antibodies, which are a marker of lifetime exposure, whereas IgM antibodies are a marker of acute/recent exposure, persistent infection, or reinfection. We performed a meta-analysis of T. gondii IgM antibodies and acute psychosis, to further investigate whether infections may be associated with relapse in schizophrenia.
Related JoVE Video
Antisense RNA amplification for target assessment of total mRNA from a single cell.
Cold Spring Harb Protoc
PUBLISHED: 11-05-2014
Show Abstract
Hide Abstract
This protocol describes how to amplify mRNA isolated from a single cell and then analyze its gene expression profile using polymerase chain reaction (PCR). Single-cell analysis is advantageous over studies of cell populations because it allows identification of a range of normal physiological states expressed by different cells of the same cell type without the confounding effects of averaging that result from measuring physiological states of cell populations. This is especially important when addressing questions of physiology in tissues, which comprises many different cell types. However, a single cell does not contain enough mRNA for all of the expressed transcripts to be detected or measured by any current molecular biology techniques. The antisense RNA (aRNA) amplification method was developed to amplify the picogram amounts of mRNA found within a single cell to microgram amounts of aRNA after three rounds of amplification. This aRNA can then easily be analyzed by microarray or next-generation sequencing. These methods allow identification of all expressed mRNA species within a single cell, including previously unknown mRNAs or those mRNAs specifically affected by a certain treatment. mRNA species of interest identified by these techniques can be further analyzed by designing primers targeting these species and performing PCR. cDNA synthesized from RNA at any stage in the aRNA amplification procedure, including material directly from collected unamplified cells, can be analyzed using PCR. Regardless of downstream applications, single-cell aRNA amplification is a powerful tool for studying single-cell physiological dynamics.
Related JoVE Video
Divergence of RNA localization between rat and mouse neurons reveals the potential for rapid brain evolution.
BMC Genomics
PUBLISHED: 09-23-2014
Show Abstract
Hide Abstract
Neurons display a highly polarized architecture. Their ability to modify their features under intracellular and extracellular stimuli, known as synaptic plasticity, is a key component of the neurochemical basis of learning and memory. A key feature of synaptic plasticity involves the delivery of mRNAs to distinct sub-cellular domains where they are locally translated. Regulatory coordination of these spatio-temporal events is critical for synaptogenesis and synaptic plasticity as defects in these processes can lead to neurological diseases. In this work, using microdissected dendrites from primary cultures of hippocampal neurons of two mouse strains (C57BL/6 and Balb/c) and one rat strain (Sprague-Dawley), we investigate via microarrays, subcellular localization of mRNAs in dendrites of neurons to assay the evolutionary differences in subcellular dendritic transcripts localization.
Related JoVE Video
Quantitative levels of aripiprazole parent drug and metabolites in urine.
Psychopharmacology (Berl.)
PUBLISHED: 09-04-2014
Show Abstract
Hide Abstract
The aim of this study is to assess urine levels of aripiprazole and metabolites among patients receiving steady-state dosing of aripiprazole.
Related JoVE Video
The Use of Simulation to Teach Suicide Risk Assessment to Health Profession Trainees-Rationale, Methodology, and a Proof of Concept Demonstration with a Virtual Patient.
Acad Psychiatry
PUBLISHED: 06-11-2014
Show Abstract
Hide Abstract
There is increasing use of educational technologies in medical and surgical specialties. Described herein is the development and application of an interactive virtual patient (VP) to teach suicide risk assessment to health profession trainees. We studied the effect of the following: (1) an interaction with a bipolar VP who attempts suicide or (2) completion of a video-teaching module on interviewing a bipolar patient, on medical students' proficiency in assessing suicide risk in standardized patients. We hypothesized that students who interact with a bipolar VP will be at least as likely to assess suicide risk, as their peers who completed a video module.
Related JoVE Video
Comparison of SGA Oral Medications and a Long-Acting Injectable SGA: The PROACTIVE Study.
Schizophr Bull
PUBLISHED: 05-30-2014
Show Abstract
Hide Abstract
Until relatively recently, long-acting injectable (LAI) formulations were only available for first-generation antipsychotics and their utilization decreased as use of oral second-generation antipsychotics (SGA) increased. Although registry-based naturalistic studies show LAIs reduce rehospitalization more than oral medications in clinical practice, this is not seen in recent randomized clinical trials. PROACTIVE (Preventing Relapse Oral Antipsychotics Compared to Injectables Evaluating Efficacy) relapse prevention study incorporated efficacy and effectiveness features. At 8 US academic centers, 305 patients with schizophrenia or schizoaffective disorder were randomly assigned to LAI risperidone (LAI-R) or physician's choice oral SGAs. Patients were evaluated during the 30-month study by masked, centralized assessors using 2-way video, and monitored biweekly by on-site clinicians and assessors who knew treatment assignment. Relapse was evaluated by a masked Relapse Monitoring Board. Differences between LAI-R and oral SGA treatment in time to first relapse and hospitalization were not significant. Psychotic symptoms and Brief Psychiatric Rating Scale total score improved more in the LAI-R group. In contrast, the LAI group had higher Scale for Assessment of Negative Symptoms Alogia scale scores. There were no other between-group differences in symptoms or functional improvement. Despite the advantage for psychotic symptoms, LAI-R did not confer an advantage over oral SGAs for relapse or rehospitalization. Biweekly monitoring, not focusing specifically on patients with demonstrated nonadherence to treatment and greater flexibility in changing medication in the oral treatment arm, may contribute to the inability to detect differences between LAI and oral SGA treatment in clinical trials.
Related JoVE Video
Effectiveness of paliperidone palmitate vs haloperidol decanoate for maintenance treatment of schizophrenia: a randomized clinical trial.
JAMA
PUBLISHED: 05-22-2014
Show Abstract
Hide Abstract
Long-acting injectable antipsychotics are used to reduce medication nonadherence and relapse in schizophrenia-spectrum disorders. The relative effectiveness of long-acting injectable versions of second-generation and older antipsychotics has not been assessed.
Related JoVE Video
Urinary tract infections in acute psychosis.
J Clin Psychiatry
PUBLISHED: 02-07-2014
Show Abstract
Hide Abstract
Schizophrenia is associated with increased infections across the lifespan. We previously found an association between urinary tract infection (UTI) and acute nonaffective psychosis. The aims of this study were to explore further the relationship between UTI and acute psychosis, including associated clinical features.
Related JoVE Video
The medical school dean: leadership and workforce development.
Acad Psychiatry
PUBLISHED: 01-16-2014
Show Abstract
Hide Abstract
The author reviews the role of deans in US academic medical centers.
Related JoVE Video
Transcriptome in vivo analysis (TIVA) of spatially defined single cells in live tissue.
Nat. Methods
PUBLISHED: 01-12-2014
Show Abstract
Hide Abstract
Transcriptome profiling of single cells resident in their natural microenvironment depends upon RNA capture methods that are both noninvasive and spatially precise. We engineered a transcriptome in vivo analysis (TIVA) tag, which upon photoactivation enables mRNA capture from single cells in live tissue. Using the TIVA tag in combination with RNA sequencing (RNA-seq), we analyzed transcriptome variance among single neurons in culture and in mouse and human tissue in vivo. Our data showed that the tissue microenvironment shapes the transcriptomic landscape of individual cells. The TIVA methodology is, to our knowledge, the first noninvasive approach for capturing mRNA from live single cells in their natural microenvironment.
Related JoVE Video
Serotonergic neuron regulation informed by in vivo single-cell transcriptomics.
FASEB J.
PUBLISHED: 11-05-2013
Show Abstract
Hide Abstract
Despite the recognized importance of the dorsal raphe (DR) serotonergic (5-HT) nuclei in the pathophysiology of depression and anxiety, the molecular components/putative drug targets expressed by these neurons are poorly characterized. Utilizing the promoter of an ETS domain transcription factor that is a stable marker of 5-HT neurons (Pet-1) to drive 5-HT neuronal expression of YFP, we identified 5-HT neurons in live acute slices. We isolated RNA from single 5-HT neurons in the ventromedial and lateral wings of the DR and performed single-cell RNA-Seq analysis identifying >500 G-protein coupled receptors (GPCRs) including receptors for classical transmitters, lipid signals, and peptides as well as dozens of orphan-GPCRs. Using these data to inform our selection of receptors to assess, we found that oxytocin and lysophosphatidic acid 1 receptors are translated and active in costimulating, with the ?1-adrenergic receptor, the firing of DR 5-HT neurons, while the effects of histamine are inhibitory and exerted at H3 histamine receptors. The inhibitory histamine response provides evidence for tonic in vivo histamine inhibition of 5-HT neurons. This study illustrates that unbiased single-cell transcriptomics coupled with functional analyses provides novel insights into how neurons and neuronal systems are regulated.-Spaethling, J. M., Piel, D., Dueck, H., Buckley, P. T., Morris, J. F., Fisher, S. A., Lee, J., Sul, J.-Y., Kim, J., Bartfai, T., Beck, S. G., Eberwine, J. H. Serotonergic neuron regulation informed by in vivo single-cell transcriptomics.
Related JoVE Video
High-dose oral ziprasidone versus conventional dosing in schizophrenia patients with residual symptoms: the ZEBRAS study.
J Clin Psychopharmacol
PUBLISHED: 06-19-2013
Show Abstract
Hide Abstract
Uncontrolled studies have suggested that increasing the dose of ziprasidone above the standard maximum daily dose of 160 mg may be more effective for some patients with schizophrenia. To test this hypothesis, we conducted an 8-week, placebo-controlled, fixed-dose escalation trial comparing ziprasidone 160 versus 320 mg/d in individuals with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks. Of 75 randomized patients, 42 completed the study. Serum ziprasidone concentrations increased significantly in the high-dose group compared with the standard-dose group at week 4 but did not differ between groups at week 8. Both treatment groups exhibited significant symptomatic improvement. Response did not differ between treatment groups; however, in the high-dose group, higher ziprasidone serum concentrations were associated with better response at a trend level. Higher ziprasidone concentrations were also associated with reductions in diastolic blood pressure and, at a trend level, with more prominent negative symptoms and greater QTc prolongation. In summary, increasing the ziprasidone dose to 320 mg/d did not produce a sustained elevation in serum concentrations or symptomatic improvement compared with a standard ziprasidone dose of 160 mg/d.
Related JoVE Video
Does a latent class underlie schizotypal personality disorder? Implications for schizophrenia.
J Abnorm Psychol
PUBLISHED: 05-30-2013
Show Abstract
Hide Abstract
Despite growing enthusiasm for dimensional models of personality pathology, the taxonic versus dimensional status of schizotypal personality disorder (PD) remains a point of contention in modern psychiatry. The current study aimed to determine empirically the latent structure of schizotypal PD. We examined the latent structure of schizotypal PD in the Psychiatric Morbidity Survey in Great Britain and the second wave of the U.S.-based National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) survey. We analyzed composite indicators created from participant responses using the mean above minus mean below a cut (MAMBAC), Maximum Covariance (MAXCOV), and latent mode factor analysis (L-Mode) taxometric procedures. We also analyzed item-level responses using two latent variable mixture models--latent class analysis and latent class factor analysis. Taxometric and latent variable mixture analyses supported a dimensional, rather than taxonic, structure in both epidemiological samples. The dimensional model better predicted psychosis, intellectual functioning, disability, and treatment seeking than the categorical model based on DSM-IV diagnosis. People meeting criteria for schizotypal PD appear to exist on a spectrum of severity with the rest of the population. The possible dimensionality of schizotypal PD adds to growing support for a dimensional structure of PDs including other Cluster A disorders.
Related JoVE Video
A prevalence study of urinary tract infections in acute relapse of schizophrenia.
J Clin Psychiatry
PUBLISHED: 04-09-2013
Show Abstract
Hide Abstract
Schizophrenia is associated with immune abnormalities and increased mortality from infectious diseases. The aim of this study was to examine whether acute relapse of schizophrenia was associated with urinary tract infection (UTI), in comparison with controls, after controlling for potential confounding factors.
Related JoVE Video
A systematic, quantitative review of blood autoantibodies in schizophrenia.
Schizophr. Res.
PUBLISHED: 04-02-2013
Show Abstract
Hide Abstract
Schizophrenia is associated with immune system dysfunction, including an increased prevalence of autoimmune disorders and autoantibodies. We performed a systematic, quantitative review of self-reacting blood antibodies in patients with schizophrenia.
Related JoVE Video
Biomarkers in schizophrenia: a brief conceptual consideration.
Dis. Markers
PUBLISHED: 04-01-2013
Show Abstract
Hide Abstract
Biomarkers have been sought after in the field of schizophrenia research for decades. In this paper, we discuss some of the concepts around developing biomarkers in an effort to understand why the use of biomarkers for schizophrenia has not been realized. In particular, we address the following 4 questions. Why would we need a diagnostic biomarker for schizophrenia? How is a biomarker typically defined and how does that influence the discovery of biomarkers in schizophrenia? What is the best use of biomarkers in schizophrenia? Do any biomarkers for schizophrenia currently exist? Thus, while we suggest that no biomarker currently exists for schizophrenia, the heterogeneity associated with schizophrenia will most likely need to be taken into account which will result in multiple biomarkers that identify the multiple underlying pathophysiological processes involved in schizophrenia. Therefore, much additional work will be required prior to obtaining any well-established biomarkers for schizophrenia.
Related JoVE Video
Meta-analysis of oxidative stress in schizophrenia.
Biol. Psychiatry
PUBLISHED: 03-20-2013
Show Abstract
Hide Abstract
Schizophrenia is associated with impaired antioxidant defense, including abnormal serum, plasma, and red blood cell (RBC) oxidative stress parameters. We performed a meta-analysis of these associations, considering the effect of clinical status and antipsychotic treatment after an acute exacerbation of psychosis.
Related JoVE Video
Cytoplasmic intron retention, function, splicing, and the sentinel RNA hypothesis.
Wiley Interdiscip Rev RNA
PUBLISHED: 03-13-2013
Show Abstract
Hide Abstract
Cytoplasmic splicing represents a newly emerging level of transcriptional regulation adding to the molecular diversity of mammalian cells. As examples of this noncanonical form of transcript processing are discovered, the evidence of its importance to normal cellular function grows. Work from a number of groups using a variety of cell types is steadily identifying a large number of transcripts (and soon to be even larger as genome-wide analyses of retained introns across a number of cellular phenotypes are currently underway) that undergo some level of regulated endogenous extranuclear splicing as part of their normal biosynthetic pathway. Here, we review the existing data covering cytoplasmic retained intron sequences and suggest that such sequences may be a component of sentinel RNA that serves to generate transcript variants within the cytoplasm as well as a source for RNA-based secondary messages. For further resources related to this article, please visit the WIREs website. Conflict of interest: The authors have declared no conflicts of interest for this article.
Related JoVE Video
Pharmacological characterization of GSK573719 (umeclidinium): a novel, long-acting, inhaled antagonist of the muscarinic cholinergic receptors for treatment of pulmonary diseases.
J. Pharmacol. Exp. Ther.
PUBLISHED: 02-22-2013
Show Abstract
Hide Abstract
Activation of muscarinic subtype 3 (M3) muscarinic cholinergic receptors (mAChRs) increases airway tone, whereas its blockade improves lung function and quality of life in patients with pulmonary diseases. The present study evaluated the pharmacological properties of a novel mAChR antagonist, GSK573719 (4-[hydroxy(diphenyl)methyl]-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicyclo[2.2.2]octane; umeclidinium). The affinity (Ki) of GSK573719 for the cloned human M1-M5 mAChRs ranged from 0.05 to 0.16 nM. Dissociation of [(3)H]GSK573719 from the M3 mAChR was slower than that for the M2 mAChR [half-life (t1/2) values: 82 and 9 minutes, respectively]. In Chinese hamster ovary cells transfected with recombinant human M3 mAChRs, GSK573719 demonstrated picomolar potency (-log pA2 = 23.9 pM) in an acetylcholine (Ach)-mediated Ca(2+) mobilization assay. Concentration-response curves indicate competitive antagonism with partial reversibility after drug washout. Using isolated human bronchial strips, GSK573719 was also potent and showed competitive antagonism (-log pA2 = 316 pM) versus carbachol, and was slowly reversible in a concentration-dependent manner (1-100 nM). The time to 50% restoration of contraction at 10 nM was about 381 minutes (versus 413 minutes for tiotropium bromide). In mice, the ED50 value was 0.02 ?g/mouse intranasally. In conscious guinea pigs, intratracheal administration of GSK573719 dose dependently blocked Ach-induced bronchoconstriction with long duration of action, and was comparable to tiotropium; 2.5 ?g elicited 50% bronchoprotection for >24 hours. Thus, GSK573719 is a potent anticholinergic agent that demonstrates slow functional reversibility at the human M3 mAChR and long duration of action in animal models. This pharmacological profile translated into a 24-hour duration of bronchodilation in vivo, which suggested umeclidinium will be a once-daily inhaled treatment of pulmonary diseases.
Related JoVE Video
The genomic psychiatry cohort: partners in discovery.
Am. J. Med. Genet. B Neuropsychiatr. Genet.
PUBLISHED: 02-19-2013
Show Abstract
Hide Abstract
The Genomic Psychiatry Cohort (GPC) is a longitudinal resource designed to provide the necessary population-based sample for large-scale genomic studies, studies focusing on Research Domain Criteria (RDoC) and/or other alternate phenotype constructs, clinical and interventional studies, nested case-control studies, long-term disease course studies, and genomic variant-to-phenotype studies. We provide and will continue to encourage access to the GPC as an international resource. DNA and other biological samples and diagnostic data are available through the National Institute of Mental Health (NIMH) Repository. After appropriate review and approval by an advisory board, investigators are able to collaborate in, propose, and co-lead studies involving cohort participants.
Related JoVE Video
Neuroimaging schizophrenia: a picture is worth a thousand words, but is it saying anything important?
Curr Psychiatry Rep
PUBLISHED: 02-12-2013
Show Abstract
Hide Abstract
Schizophrenia is characterized by neurostructural and neurofunctional aberrations that have now been demonstrated through neuroimaging research. The article reviews recent studies that have attempted to use neuroimaging to understand the relation between neurological abnormalities and aspects of the phenomenology of schizophrenia. Neuroimaging studies show that neurostructural and neurofunctional abnormalities are present in people with schizophrenia and their close relatives and may represent putative endophenotypes. Neuroimaging phenotypes predict the emergence of psychosis in individuals classified as high-risk. Neuroimaging studies have linked structural and functional abnormalities to symptoms; and progressive structural changes to clinical course and functional outcome. Neuroimaging has successfully indexed the neurotoxic and neuroprotective effects of schizophrenia treatments. Pictures can inform about aspects of the phenomenology of schizophrenia including etiology, onset, symptoms, clinical course, and treatment effects but this assertion is tempered by the scientific and practical limitations of neuroimaging.
Related JoVE Video
A psychometric study of recovery among Certified Peer Specialists.
Psychiatry Res
PUBLISHED: 01-21-2013
Show Abstract
Hide Abstract
The recovery model is wielding a welcome influence in the mental healthcare system. Despite its potential impact, systematic studies of the recovery construct as viewed by consumers and former consumers of mental health services have only recently begun to permeate the literature. We have embarked on an ongoing collaboration with the Georgia Mental Health Consumer Network to study the recovery experiences of Certified Peer Specialists (CPSs). As a first step, we evaluated the psychometric characteristics of a new measure of the recovery construct in CPSs. CPSs (N=84) enrolled in the GMHCN completed the Maryland Assessment of Recovery in Serious Mental Illness (MARS) along with measures of resilience, coping styles, community living, social support, internalized stigma, psychopathology, and personality. Recovery as measured by the MARS was associated with resilience, coping behaviors, quality of social support, community living, internalized stigma, and severity of psychopathology. Recovery did not demonstrate a statistically significant association with personality. Recovery appeared to mediate the effect of psychopathology and episodic stressors on community functioning. Our psychometric study supports the psychometric soundness of the MARS and the construct validity of recovery.
Related JoVE Video
Subcellular RNA sequencing reveals broad presence of cytoplasmic intron-sequence retaining transcripts in mouse and rat neurons.
PLoS ONE
PUBLISHED: 01-01-2013
Show Abstract
Hide Abstract
Recent findings have revealed the complexity of the transcriptional landscape in mammalian cells. One recently described class of novel transcripts are the Cytoplasmic Intron-sequence Retaining Transcripts (CIRTs), hypothesized to confer post-transcriptional regulatory function. For instance, the neuronal CIRT KCNMA1i16 contributes to the firing properties of hippocampal neurons. Intronic sub-sequence retention within IL1-? mRNA in anucleate platelets has been implicated in activity-dependent splicing and translation. In a recent study, we showed CIRTs harbor functional SINE ID elements which are hypothesized to mediate dendritic localization in neurons. Based on these studies and others, we hypothesized that CIRTs may be present in a broad set of transcripts and comprise novel signals for post-transcriptional regulation. We carried out a transcriptome-wide survey of CIRTs by sequencing micro-dissected subcellular RNA fractions. We sequenced two batches of 150-300 individually dissected dendrites from primary cultures of hippocampal neurons in rat and three batches from mouse hippocampal neurons. After statistical processing to minimize artifacts, we found a broad prevalence of CIRTs in the neurons in both species (44-60% of the expressed transcripts). The sequence patterns, including stereotypical length, biased inclusion of specific introns, and intron-intron junctions, suggested CIRT-specific nuclear processing. Our analysis also suggested that these cytoplasmic intron-sequence retaining transcripts may serve as a primary transcript for ncRNAs. Our results show that retaining intronic sequences is not isolated to a few loci but may be a genome-wide phenomenon for embedding functional signals within certain mRNA. The results hypothesize a novel source of cis-sequences for post-transcriptional regulation. Our results hypothesize two potentially novel splicing pathways: one, within the nucleus for CIRT biogenesis; and another, within the cytoplasm for removing CIRT sequences before translation. We also speculate that release of CIRT sequences prior to translation may form RNA-based signals within the cell potentially comprising a novel class of signaling pathways.
Related JoVE Video
Lipidomics reveals early metabolic changes in subjects with schizophrenia: effects of atypical antipsychotics.
PLoS ONE
PUBLISHED: 01-01-2013
Show Abstract
Hide Abstract
There is a critical need for mapping early metabolic changes in schizophrenia to capture failures in regulation of biochemical pathways and networks. This information could provide valuable insights about disease mechanisms, trajectory of disease progression, and diagnostic biomarkers. We used a lipidomics platform to measure individual lipid species in 20 drug-naïve patients with a first episode of schizophrenia (FE group), 20 patients with chronic schizophrenia that had not adhered to prescribed medications (RE group), and 29 race-matched control subjects without schizophrenia. Lipid metabolic profiles were evaluated and compared between study groups and within groups before and after treatment with atypical antipsychotics, risperidone and aripiprazole. Finally, we mapped lipid profiles to n3 and n6 fatty acid synthesis pathways to elucidate which enzymes might be affected by disease and treatment. Compared to controls, the FE group showed significant down-regulation of several n3 polyunsaturated fatty acids (PUFAs), including 20:5n3, 22:5n3, and 22:6n3 within the phosphatidylcholine and phosphatidylethanolamine lipid classes. Differences between FE and controls were only observed in the n3 class PUFAs; no differences where noted in n6 class PUFAs. The RE group was not significantly different from controls, although some compositional differences within PUFAs were noted. Drug treatment was able to correct the aberrant PUFA levels noted in FE patients, but changes in re patients were not corrective. Treatment caused increases in both n3 and n6 class lipids. These results supported the hypothesis that phospholipid n3 fatty acid deficits are present early in the course of schizophrenia and tend not to persist throughout its course. These changes in lipid metabolism could indicate a metabolic vulnerability in patients with schizophrenia that occurs early in development of the disease.
Related JoVE Video
Psychopharmacology of aggression in schizophrenia.
Schizophr Bull
PUBLISHED: 08-24-2011
Show Abstract
Hide Abstract
The management of aggression in patients with schizophrenia is a complex and challenging clinical dilemma. It also is greatly influenced by prevailing societal and medicolegal considerations regarding the perceived associations between violence and mental illness. This article provides a succinct account of a complex area and offers evidence for available treatments to reduce the occurrence of violent behavior among patients with schizophrenia.
Related JoVE Video
Drug targets: single-cell transcriptomics hastens unbiased discovery.
Trends Pharmacol. Sci.
PUBLISHED: 03-31-2011
Show Abstract
Hide Abstract
Drug discovery in neuro- and psychopharmacology is lagging, and the most commonly mentioned cause is the scarcity of drug targets. Using NextGen sequencing based single-cell transcriptomics (SBSCT), several hundred different receptors and channels can be identified in individual neurons, and the functional gene product can subsequently be validated. The use of single-cell transcriptome data to reveal the entire receptor repertoire is crucial, as the copy numbers of mRNAs encoding receptors are low, and when cells are pooled dilution of rare mRNAs leads to loss of signal. These overlooked receptors on key neurons often mediate robust effects that may be therapeutically useful. SBSCT also enables the identification of orphan receptors and can provide strong evidence for receptor heterodimers. Here, we compare SBSCT to other single-cell profiling methods. We argue that the unbiased nature of SBSCT makes it a powerful tool for the identification of new drug targets.
Related JoVE Video
Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects.
Biol. Psychiatry
PUBLISHED: 03-21-2011
Show Abstract
Hide Abstract
Schizophrenia is associated with immune system dysfunction, including aberrant cytokine levels. We performed a meta-analysis of these associations, considering effects of clinical status and antipsychotic treatment following an acute illness exacerbation.
Related JoVE Video
A propitious moment in the midst of crisis: a case study of organizational change in an academic department.
Acad Psychiatry
PUBLISHED: 03-16-2011
Show Abstract
Hide Abstract
The authors analyze the change, growth, and healing process of the Department of Psychiatry and Health Behavior at the Medical College of Georgia School of Medicine, which came close to its demise when the department Chair and a senior faculty member were arrested and charged with criminal misconduct related to financial transactions in the department.
Related JoVE Video
Turnover of first-time Chairs in departments of psychiatry.
Acad Psychiatry
PUBLISHED: 03-16-2011
Show Abstract
Hide Abstract
The authors examine the tenure of first-time Chairs in academic departments of psychiatry in order to stimulate discussion on extant workforce and leadership issues.
Related JoVE Video
Leadership experiences and characteristics of chairs of academic departments of psychiatry.
Acad Psychiatry
PUBLISHED: 03-16-2011
Show Abstract
Hide Abstract
Effective leadership in academic medicine requires a broad constellation of skills, experiences, and core values. The authors sought to describe and define these.
Related JoVE Video
Pharmacotherapy for treatment-refractory schizophrenia.
Expert Opin Pharmacother
PUBLISHED: 01-25-2011
Show Abstract
Hide Abstract
despite advances in pharmacotherapy of schizophrenia-spectrum disorders, a large percentage of persons with schizophrenia remain at least partially nonresponsive to treatment, leading to increased morbidity/mortality, increased healthcare cost, and poor quality of life for affected individuals.
Related JoVE Video
Brain-derived neurotrophic factor: findings in schizophrenia.
Curr Opin Psychiatry
PUBLISHED: 01-21-2011
Show Abstract
Hide Abstract
To review the role of brain-derived neurotrophic factor (BDNF) in neuroplasticity related to schizophrenia and the recent findings that have been reported on the status of BDNF in patients with schizophrenia and its association with the clinical measures.
Related JoVE Video
Cytoplasmic intron sequence-retaining transcripts can be dendritically targeted via ID element retrotransposons.
Neuron
PUBLISHED: 01-20-2011
Show Abstract
Hide Abstract
RNA precursors give rise to mRNA after splicing of intronic sequences traditionally thought to occur in the nucleus. Here, we show that intron sequences are retained in a number of dendritically-targeted mRNAs, by using microarray and Illumina sequencing of isolated dendritic mRNA as well as in situ hybridization. Many of the retained introns contain ID elements, a class of SINE retrotransposon. A portion of these SINEs confers dendritic targeting to exogenous and endogenous transcripts showing the necessity of ID-mediated mechanisms for the targeting of different transcripts to dendrites. ID elements are capable of selectively altering the distribution of endogenous proteins, providing a link between intronic SINEs and protein function. As such, the ID element represents a common dendritic targeting element found across multiple RNAs. Retention of intronic sequence is a more general phenomenon than previously thought and plays a functional role in the biology of the neuron, partly mediated by co-opted repetitive sequences.
Related JoVE Video
New-age patient communications through social networks.
Gen Hosp Psychiatry
PUBLISHED: 01-13-2011
Show Abstract
Hide Abstract
Suicide prevention continues to be a significant clinical challenge in the care of psychiatric patients, particularly among youth. New patterns of interactions and communications using online social networks create opportunities for persons to indicate their mood, their opinions, and also to express ideation and plans about suicide. We report a case of a suicide attempt and how communications through online social networks initiated treatment and affected its outcome. We discuss advantages and challenges to clinicians regarding use social networks and electronic communication in patient care.
Related JoVE Video
Intron retention facilitates splice variant diversity in calcium-activated big potassium channel populations.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 11-15-2010
Show Abstract
Hide Abstract
We report that the stress axis-regulated exon (STREX)-containing calcium-activated big potassium (BKCa) channel splice variant expression and physiology are regulated in part by cytoplasmic splicing and intron retention. NextGen sequencing of the mRNA complement of pooled hippocampal dendrite samples found intron 17a (i17a), the intron immediately preceding STREX, in the BKCa mRNA. Further molecular analyses of i17a revealed that the majority of i17a-containing BKCa channel mRNAs associate with STREX. i17a siRNA treatment followed by STREX protein immunocytochemistry demonstrated both reduced levels and altered subcellular distribution of STREX-containing BKCa channel protein. Selective reduction of i17a-BKCa or STREX-BKCa mRNAs induced similar changes in the burst firing properties of hippocampal neurons. Collectively, these data show that STREX splice variant regulation via cytoplasmic splicing and intron retention helps generate STREX-dependent BKCa current diversity in hippocampal neurons.
Related JoVE Video
mRNA for the EAAC1 subtype of glutamate transporter is present in neuronal dendrites in vitro and dramatically increases in vivo after a seizure.
Neurochem. Int.
PUBLISHED: 09-22-2010
Show Abstract
Hide Abstract
The neuronal Na(+)-dependent glutamate transporter, excitatory amino acid carrier 1 (EAAC1, also called EAAT3), has been implicated in the control of synaptic spillover of glutamate, synaptic plasticity, and the import of cysteine for neuronal synthesis of glutathione. EAAC1 protein is observed in both perisynaptic regions of the synapse and in neuronal cell bodies. Although amino acid residues in the carboxyl terminal tail have been implicated in the dendritic targeting of EAAC1 protein, it is not known if mRNA for EAAC1 may also be targeted to dendrites. Sorting of mRNA to specific cellular domains provides a mechanism by which signals can rapidly increase translation in a local environment; this form of regulated translation has been linked to diverse biological phenomena ranging from establishment of polarity during embryogenesis to synapse development and synaptic plasticity. In the present study, EAAC1 mRNA sequences were amplified from dendritic samples that were mechanically harvested from low-density hippocampal neuronal cultures. In parallel analyses, mRNA for histone deacetylase 2 (HDAC-2) and glial fibrillary acidic protein (GFAP) was not detected, suggesting that these samples are not contaminated with cell body or glial mRNAs. EAAC1 mRNA also co-localized with Map2a (a marker of dendrites) but not Tau1 (a marker of axons) in hippocampal neuronal cultures by in situ hybridization. In control rats, EAAC1 mRNA was observed in soma and proximal dendrites of hippocampal pyramidal neurons. Following pilocarpine- or kainate-induced seizures, EAAC1 mRNA was present in CA1 pyramidal cell dendrites up to 200?m from the soma. These studies provide the first evidence that EAAC1 mRNA localizes to dendrites and suggest that dendritic targeting of EAAC1 mRNA is increased by seizure activity and may be regulated by neuronal activity/depolarization.
Related JoVE Video
Pharmacogenetics and schizophrenia.
Clin. Lab. Med.
PUBLISHED: 09-14-2010
Show Abstract
Hide Abstract
The wide interindividual variability in clinical response and tolerability of antipsychotic medications has led investigators to postulate that these variabilities may be under genetic control. Although not always consistent, there are promising indications from emergent pharmacogenetic studies that efficacy of antipsychotic medications for the various symptom domains of psychopathology in schizophrenia may be genetically regulated. This is an encouraging approach. Moreover, there are also suggestive findings that the side-effect profiles of second-generation antipsychotic medications and their propensity to cause weight gain and glucose and lipid abnormalities as well as tardive dyskinesia may be related to pharmacogenetic factors in this patient population. Ultimately, such approaches could drive choices of antipsychotic medication based on the likelihood of clinical response and development of side effects in light of a particular patients genetic profile. In the future, this targeted approach (personalized medicine) may become informative for clinicians choosing an antipsychotic medication for an individual patient with schizophrenia.
Related JoVE Video
A double-blind, randomized study comparing the efficacy and safety of sertindole and risperidone in patients with treatment-resistant schizophrenia.
J Clin Psychiatry
PUBLISHED: 07-27-2010
Show Abstract
Hide Abstract
The comparative efficacy of second-generation antipsychotics has yet to be fully elucidated in patients with treatment-resistant schizophrenia. The objective of this study was to examine the efficacy and safety of sertindole, compared to risperidone, in this patient population.
Related JoVE Video
Minor physical anomalies: potentially informative vestiges of fetal developmental disruptions in schizophrenia.
Int. J. Dev. Neurosci.
PUBLISHED: 07-13-2010
Show Abstract
Hide Abstract
Minor physical anomalies (MPAs) are subtle signs of developmental deviation that are observed at an elevated frequency among patients with schizophrenia. These minor morphological abnormalities of the craniofacial region and limbs arise during fetal development and represent a set of risk markers for schizophrenia. Although MPAs are not specific to schizophrenia, established findings about MPAs vis-à-vis schizophrenia include the replicated findings that MPAs are more prevalent among individuals with schizophrenia than healthy controls, MPAs are more prevalent among individuals with schizophrenia than unaffected relatives, and MPAs are not consistently associated with symptom domains or other risk markers, such as neurological soft signs. Unresolved questions include whether or not MPAs are more prevalent among unaffected relatives than healthy controls, and which specific MPAs are most associated with schizophrenia. This overview presents three promising avenues of further research on MPAs, including: (1) studies relying on traditional summary scores that combine multiple MPAs, which may have a role in prospective risk stratification in conjunction with other risk markers and endophenotypes; (2) research on specific, quantitatively assessed MPAs (especially in specific craniofacial structures) that may inform neurodevelopmental understandings of schizophrenia; and (3) genetic studies aimed at identifying the heritable and nonheritable determinants of specific MPAs, which may increase the fields understanding of the origins of MPAs and the nature of their association with schizophrenia.
Related JoVE Video
Generic penetration in the retail atypical antipsychotic market.
Psychiatry (Edgmont)
PUBLISHED: 05-04-2010
Show Abstract
Hide Abstract
In this article, we explore the penetration of generic atypical antipsychotics in the United States market before and after the availability of generic risperidone in July 2008. Analysis suggests that, overall, generic penetration into the atypical antipsychotic market has grown from approximately three percent in January 2008 to more than 25 percent in December 2009. Similar trends are uncovered when branded and generic prescriptions are analyzed by specialty.
Related JoVE Video
State hospital-university collaborations: a 25-year follow-up.
Acad Psychiatry
PUBLISHED: 03-13-2010
Show Abstract
Hide Abstract
A formative survey of psychiatry departments 25 years ago showed strong and valued relationships between these departments and state hospitals. The authors sought to evaluate the extent of present-day collaborative relationships.
Related JoVE Video
Can acute overdose of metformin lead to lactic acidosis?
Am J Emerg Med
PUBLISHED: 01-28-2010
Show Abstract
Hide Abstract
Metformin-associated lactic acidosis (MALA) is well described in patients taking therapeutic metformin who develop renal failure or other serious comorbid conditions. Metformin-associated lactic acidosis from acute overdose has also been described in case series but is debated by some clinicians, arguing that metformin overdose does not cause lactic acidosis. Our aim was to perform a multicenter poison control database review to determine if MALA can occur in mono-overdose patients with no comorbid conditions.
Related JoVE Video
Evaluation of akathisia in patients with schizophrenia, schizoaffective disorder, or bipolar I disorder: a post hoc analysis of pooled data from short- and long-term aripiprazole trials.
J. Psychopharmacol. (Oxford)
PUBLISHED: 12-14-2009
Show Abstract
Hide Abstract
The objective of this article is to assess the clinical characteristics of akathisia in patients with schizophrenia, schizoaffective disorder, or bipolar I disorder receiving aripiprazole, haloperidol, olanzapine, or placebo. We conducted post hoc analyses of pooled safety data from trials in patients with schizophrenia, schizoaffective disorder, and bipolar I disorder. Outcome measures included the incidence of akathisia, time to onset, duration, severity, and discontinuation due to akathisia, concomitant use of benzodiazepines and/or anticholinergics, Barnes Akathisia Rating Scale (BARS) scores, and the correlation between antipsychotic efficacy and akathisia. The results for schizophrenia and schizoaffective disorder were as follows: akathisia in 9% of aripiprazole- and 6% of placebo-treated patients; 12.5% of aripiprazole- versus 24% of haloperidol-treated patients; 11% of aripiprazole- versus 6% of olanzapine-treated patients. Bipolar I disorder: akathisia in 18% of aripiprazole- and 5% of placebo-treated patients. The clinical characteristics of akathisia were similar between each data set, regardless of disease. Akathisia was generally mild-to-moderate in severity. Discontinuation due to akathisia was low in both the schizophrenia trials (aripiprazole 0.3%; placebo 0%; aripiprazole 0.9%; haloperidol 2.3%; aripiprazole 1.2%; olanzapine 0.2%) and the bipolar trials (aripiprazole 2.3%; placebo 0%). Treatment-emergent akathisia was not associated with a poorer clinical response. In conclusion, akathisia with aripiprazole occurred early in treatment, was mild-to-moderate in severity, led to few study discontinuations, and did not compromise therapeutic efficacy.
Related JoVE Video
Defining "good" and "poor" outcomes in patients with schizophrenia or schizoaffective disorder: a multidimensional data-driven approach.
Psychiatry Res
PUBLISHED: 11-08-2009
Show Abstract
Hide Abstract
The studys goal was to characterize the typology of patient outcomes based on social and occupational functioning and psychiatric symptoms following antipsychotic drug treatment, and to explore predictors of group membership representing the best/worst outcomes. A hierarchical cluster analysis was used to define groups of patients (n=1449) based on endpoint values for psychiatric symptoms, social functioning, and useful work measured up to 30 weeks of treatment. Stepwise logistic regression was used to construct predictive models of cluster membership for baseline predictors, and with 2/4/8 weeks of treatment. Five distinct clusters of patients were identified at endpoint (Clusters A-E). Patients in Cluster A (25.6%, best outcome) had minimal psychiatric symptoms and mild functional impairment, while patients in Cluster D (14.3%) and E (14.8%) (worst outcome) had moderate-to-severe symptoms and severe functional impairment. Occupational functioning, disorganized thinking, and positive symptoms were sufficient to describe the clusters. Membership in the best/worst clusters was predicted by baseline scores for functioning and symptom severity, and by early changes in symptoms with treatment. Psychiatric symptoms and functioning provided complementary information to describe treatment outcomes. Early symptom response significantly improved the prediction of outcome, suggesting that early monitoring of treatment response may be useful in clinical practice.
Related JoVE Video
Insulin causes hyperthermia by direct inhibition of warm-sensitive neurons.
Diabetes
PUBLISHED: 10-21-2009
Show Abstract
Hide Abstract
Temperature and nutrient homeostasis are two interdependent components of energy balance regulated by distinct sets of hypothalamic neurons. The objective is to examine the role of the metabolic signal insulin in the control of core body temperature (CBT).
Related JoVE Video
Treatment of schizoaffective disorder.
Psychiatry (Edgmont)
PUBLISHED: 09-03-2009
Show Abstract
Hide Abstract
In this article, we investigate the range of treatments prescribed for schizoaffective disorder. The data show that the majority of those treated, 87 percent, receive two or more pharmaceutical classes. From a therapeutic class perspective, 93 percent of schizoaffective disorder patients receive an antipsychotic, 48 percent receive a mood disorder treatment, and 42 percent receive an antidepressant. An expert commentary is also included.
Related JoVE Video
The reduced folate carrier (SLC19A1) c.80G>A polymorphism is associated with red cell folate concentrations among women.
Ann. Hum. Genet.
PUBLISHED: 07-28-2009
Show Abstract
Hide Abstract
Low folate status may be a consequence of suboptimal intake, transport or cellular utilization of folate and, together with elevated homocysteine, is a recognized risk factor or marker for several human pathologies. As folate transport across cell membranes is mediated in part by the reduced folate carrier (RFC1), variants within SLC19A1, the gene that encodes RFC1, may influence disease risk via an effect on folate and/or homocysteine levels. The present study was undertaken to assess the association between the SLC19A1 c.80G>A polymorphism and folate/homocysteine concentrations in healthy young adults from Northern Ireland. The SLC19A1 c.80G>A polymorphism was not strongly associated with either serum folate or homocysteine concentrations in either men or women. However, in women, but not in men, this polymorphism explained 5% of the variation in red blood cell (RBC) folate levels (P= 0.02). Relative to women with the SLC19A1 c.80GG genotype, women with the GA and AA genotypes had higher RBC folate concentrations. Consequently, compared to women with the SLC19A1 c.80GA and AA genotypes, women who are homozygous for the 80G allele may be at increased risk of having a child affected with a neural tube defect and of developing pathologies that have been associated with folate insufficiency, such as cardiovascular disease.
Related JoVE Video
Psychiatric comorbidities and schizophrenia.
Schizophr Bull
PUBLISHED: 06-13-2009
Show Abstract
Hide Abstract
Psychiatric comorbidities are common among patients with schizophrenia. Substance abuse comorbidity predominates. Anxiety and depressive symptoms are also very common throughout the course of illness, with an estimated prevalence of 15% for panic disorder, 29% for posttraumatic stress disorder, and 23% for obsessive-compulsive disorder. It is estimated that comorbid depression occurs in 50% of patients, and perhaps (conservatively) 47% of patients also have a lifetime diagnosis of comorbid substance abuse. This article chronicles these associations, examining whether these comorbidities are "more than chance" and might represent (distinct) phenotypes of schizophrenia. Among the anxiety disorders, the evidence at present is most abundant for an association with obsessive-compulsive disorder. Additional studies in newly diagnosed antipsychotic-naive patients and their first-degree relatives and searches for genetic and environmental risk factors are needed to replicate preliminary findings and further investigate these associations.
Related JoVE Video
Immersing practitioners in the recovery model: an educational program evaluation.
Community Ment Health J
PUBLISHED: 06-04-2009
Show Abstract
Hide Abstract
The ascendance of the recovery movement in mental health care has led to the development and implementation of educational curricula for mental health providers to assist in mental health care system transformation efforts. The Medical College of Georgia (MCG) partnered with the Georgia State Department of Human Resources (DHR) to develop, implement, and evaluate such an educational curriculum for providers within an academic medical institution. This effort, entitled Project GREAT, led to the creation of a curriculum based on the SAMHSA-defined (2006) critical components of recovery. As an initial evaluation of educational curriculum effectiveness, the authors examined effects of the training program on recovery-based knowledge and recovery-consistent attitudes. We also compared MCG provider knowledge and attitudes to those of a similar group of providers at a neighboring medical institution who did not receive the intervention and training. Findings generally supported the effectiveness of the intervention in increasing providers knowledge of recovery and a shift in recovery-supporting attitudes.
Related JoVE Video
Related JoVE Video
Transcriptome transfer produces a predictable cellular phenotype.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 04-20-2009
Show Abstract
Hide Abstract
Cellular phenotype is the conglomerate of multiple cellular processes involving gene and protein expression that result in the elaboration of a cells particular morphology and function. It has been thought that differentiated postmitotic cells have their genomes hard wired, with little ability for phenotypic plasticity. Here we show that transfer of the transcriptome from differentiated rat astrocytes into a nondividing differentiated rat neuron resulted in the conversion of the neuron into a functional astrocyte-like cell in a time-dependent manner. This single-cell study permits high resolution of molecular and functional components that underlie phenotype identity. The RNA population from astrocytes contains RNAs in the appropriate relative abundances that give rise to regulatory RNAs and translated proteins that enable astrocyte identity. When transferred into the postmitotic neuron, the astrocyte RNA population converts 44% of the neuronal host cells into the destination astrocyte-like phenotype. In support of this observation, quantitative measures of cellular morphology, single-cell PCR, single-cell microarray, and single-cell functional analyses have been performed. The host-cell phenotypic changes develop over many weeks and are persistent. We call this process of RNA-induced phenotype changes, transcriptome-induced phenotype remodeling.
Related JoVE Video
Discovery of (3-endo)-3-(2-cyano-2,2-diphenylethyl)-8,8-dimethyl-8-azoniabicyclo[3.2.1]octane bromide as an efficacious inhaled muscarinic acetylcholine receptor antagonist for the treatment of COPD.
Bioorg. Med. Chem. Lett.
PUBLISHED: 03-17-2009
Show Abstract
Hide Abstract
Design and syntheses of a novel series of muscarinic antagonists are reported. These efforts have culminated in the discovery of (3-endo)-3-(2-cyano-2,2-diphenylethyl)-8,8-dimethyl-8-azoniabicyclo[3.2.1]octane bromide (4a) as a potent and pan-active muscarinic antagonist as well as a functionally active compound in a murine model of bronchoconstriction. The compound has also displayed pharmacokinetic characteristics suitable for inhaled delivery.
Related JoVE Video
Metabolic profiles of second-generation antipsychotics in early psychosis: findings from the CAFE study.
Schizophr. Res.
PUBLISHED: 03-11-2009
Show Abstract
Hide Abstract
To further define the metabolic profiles of second-generation antipsychotics during the treatment of young patients with early psychosis, with a view to better inform prescribing clinicians.
Related JoVE Video
Melanocyte-like cells in the heart and pulmonary veins contribute to atrial arrhythmia triggers.
J. Clin. Invest.
PUBLISHED: 03-05-2009
Show Abstract
Hide Abstract
Atrial fibrillation is the most common clinical cardiac arrhythmia. It is often initiated by ectopic beats arising from the pulmonary veins and atrium, but the source and mechanism of these beats remains unclear. The melanin synthesis enzyme dopachrome tautomerase (DCT) is involved in intracellular calcium and reactive species regulation in melanocytes. Given that dysregulation of intracellular calcium and reactive species has been described in patients with atrial fibrillation, we investigated the role of DCT in this process. Here, we characterize a unique DCT-expressing cell population within murine and human hearts that populated the pulmonary veins, atria, and atrioventricular canal. Expression profiling demonstrated that this population expressed adrenergic and muscarinic receptors and displayed transcriptional profiles distinct from dermal melanocytes. Adult mice lacking DCT displayed normal cardiac development but an increased susceptibility to atrial arrhythmias. Cultured primary cardiac melanocyte-like cells were excitable, and those lacking DCT displayed prolonged repolarization with early afterdepolarizations. Furthermore, mice with mutations in the tyrosine kinase receptor Kit lacked cardiac melanocyte-like cells and did not develop atrial arrhythmias in the absence of DCT. These data suggest that dysfunction of melanocyte-like cells in the atrium and pulmonary veins may contribute to atrial arrhythmias.
Related JoVE Video
Risk of neuroleptic malignant syndrome in patients with bipolar disorder: a retrospective, population-based case-control study.
Int J Psychiatry Med
PUBLISHED: 01-01-2009
Show Abstract
Hide Abstract
Current data regarding risk factors of neuroleptic malignant syndrome (NMS) are limited. This study aims to examine factors associated with increased risk of NMS in patients with bipolar disorder.
Related JoVE Video
Tyrosine urea muscarinic acetylcholine receptor antagonists: achiral quaternary ammonium groups.
Bioorg. Med. Chem. Lett.
Show Abstract
Hide Abstract
Tyrosine ureas had been identified as potent muscarinic receptor antagonists with promising in vivo activity. Controlling the stereochemistry of the chiral quaternary ammonium center had proved to be a serious issue for this series, however. Herein we describe the preparation and SAR of tyrosine urea antagonists containing achiral quaternary ammonium centers. The most successful such moiety was the 2-methylimidazo[2,1-b][1,3]thiazol-7-ium group which yielded highly potent antagonists with long duration of action in an inhaled animal model of bronchoconstriction.
Related JoVE Video
Meta-analysis of lymphocytes in schizophrenia: clinical status and antipsychotic effects.
Biol. Psychiatry
Show Abstract
Hide Abstract
Schizophrenia is associated with immune system dysfunction, including abnormal blood immune cell parameters. We performed a meta-analysis of these associations, considering the effect of clinical status and antipsychotic treatment following an acute exacerbation of psychosis.
Related JoVE Video
Total and differential white blood cell counts, high-sensitivity C-reactive protein, and the metabolic syndrome in non-affective psychoses.
Brain Behav. Immun.
Show Abstract
Hide Abstract
The metabolic syndrome is highly prevalent in patients with schizophrenia, and is associated with a state of chronic, low-grade inflammation. Schizophrenia is also associated with increased inflammation, including aberrant blood levels of pro-inflammatory cytokines and high-sensitivity C-reactive protein (hsCRP). The purpose of this study is to investigate the relationship between total and differential white blood cell (WBC) counts, hsCRP, and the metabolic syndrome in patients with schizophrenia and related non-affective psychoses. Fifty-nine inpatients and outpatients age 18-70 with non-affective psychotic disorders and 22 controls participated in this cross-sectional study. Subjects had a fasting blood draw between 8 and 9 am for glucose, lipids, total and differential WBC counts, and hsCRP. Vital signs and anthropometric measures were obtained. Patients with non-affective psychosis and the metabolic syndrome had significantly higher total WBC counts, monocytes, and hsCRP levels than patients without the metabolic syndrome (p?0.04 for each). In binary logistic regression analyses, after controlling for potential confounding effects of age, race, sex, age at first hospitalization for psychosis, parental history of diabetes, smoking, and psychotropic medications, total WBC count, monocytes, and hsCRP were significant predictors of metabolic syndrome in patients (p?0.04 for each). hsCRP was also a significant predictor of increased waist circumference and triglycerides in patients (p?0.05 for each). Our findings suggest that measurement of total and differential WBC counts and hsCRP blood levels may be germane to the clinical care of patients with schizophrenia and related disorders, and support an association between inflammation and metabolic disturbance in these patients.
Related JoVE Video
Peers and peer-led interventions for people with schizophrenia.
Psychiatr. Clin. North Am.
Show Abstract
Hide Abstract
This article provides a snapshot of the nature, guiding philosophy, and empiric status of interventions for people with schizophrenia that go beyond traditional psychopharmacological and psychosocial treatments to include peer-led interventions. The authors discuss the nature and principles of peer-led interventions for people with schizophrenia and the types of peer-led interventions along with evidence of their effectiveness in fostering the recovery of people with schizophrenia and other severe mental illnesses. Focus is on 3 types of peer-led interventions: (1) mutual support/self-help, (2) consumer-operated services, and (3) peer support services.
Related JoVE Video
Reliable biomarkers and predictors of schizophrenia and its treatment.
Psychiatr. Clin. North Am.
Show Abstract
Hide Abstract
Biomarkers are chemical and physiologic parameters that can provide reliable and predictive information about the course and treatment of a given illness. Biomarkers are being increasingly sought after in other medical conditions, and in some instances (eg, breast cancer therapy) are beginning to be incorporated into clinical decision making. There is a confluence of research investigating potential biomarkers for schizophrenia. This article reviews early progress and strategies for evaluating biomarkers, as well as how this approach can advance the treatment of schizophrenia toward personalized medicine.
Related JoVE Video
Quantitative biology of single neurons.
J R Soc Interface
Show Abstract
Hide Abstract
The building blocks of complex biological systems are single cells. Fundamental insights gained from single-cell analysis promise to provide the framework for understanding normal biological systems development as well as the limits on systems/cellular ability to respond to disease. The interplay of cells to create functional systems is not well understood. Until recently, the study of single cells has concentrated primarily on morphological and physiological characterization. With the application of new highly sensitive molecular and genomic technologies, the quantitative biochemistry of single cells is now accessible.
Related JoVE Video
The current state and future possibilities of recruiting leaders of academic health centers.
Acad Med
Show Abstract
Hide Abstract
For more than 30 years, commentators have been questioning the processes that medical schools and teaching hospitals use to search and recruit their leaders. Recent studies suggest that these problems persist, not only within academic medicine but across industries and countries.The authors thesis in this article is that the search process, although always important, will be of even greater consequence than before, given the current environment for academic medicine. They (1) demonstrate why the academic medicine sector faces an impending talent crisis, (2) review the evidence on how a systematic approach to talent development has important organizational outcomes, (3) review the current state of the search and recruitment process for leaders in academic medicine centers, and (4) underscore the use of a continuous improvement approach as a way to improve the search process.The authors describe one such approach, which included retaining a core set of search committee members from one search to the next, appointing an associate dean for leadership development who instilled consistency in search and recruitment processes, and evaluating and making improvements to the search process via participant and stakeholder feedback.
Related JoVE Video
Plasma BDNF levels vary in relation to body weight in females.
PLoS ONE
Show Abstract
Hide Abstract
Brain derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of depression as well as neuropsychiatric and neurodegenerative disorders. Recent studies show a role of BDNF in energy metabolism and body weight regulation. We examined BDNF levels in plasma and cerebrospinal fluid (CSF) samples from age matched elderly depressed and control subjects. Also, the association of BDNF levels with age, gender, body weight, body mass index (BMI), and cognitive performance was evaluated. We did not find any significant differences in plasma and CSF BDNF levels between depressed and control subjects. Plasma BDNF levels were negatively correlated with age (but not with BMI and body weight), when analyses were performed including both depressed and control subjects. A significant reduction in plasma BDNF levels was observed in females as compared to male subjects, and the change in BDNF levels were significantly and positively related to body weight in females. Furthermore, significant increases in Total Recall and Delayed Recall values were found in females as compared to males. In conclusion, the lower BDNF levels observed in females suggest that changes in peripheral BDNF levels are likely secondary to an altered energy balance. However, further studies using larger sample size are warranted.
Related JoVE Video
Feasibility and pilot efficacy results from the multisite Cognitive Remediation in the Schizophrenia Trials Network (CRSTN) randomized controlled trial.
J Clin Psychiatry
Show Abstract
Hide Abstract
The true benefit of pharmacologic intervention to improve cognition in schizophrenia may not be evident without regular cognitive enrichment. Clinical trials assessing the neurocognitive effects of new medications may require engagement in cognitive remediation exercises to stimulate the benefit potential. However, the feasibility of large-scale multisite studies using cognitive remediation at clinical trials sites has not been established.
Related JoVE Video
Impaired plasmalogens in patients with schizophrenia.
Psychiatry Res
Show Abstract
Hide Abstract
Plasmalogens are a subclass of glycerophospholipids and ubiquitous constituents of cellular membranes and serum lipoproteins. Several neurological disorders show decreased level of plasmogens. An earlier study found differences in plasma phospholipids between unmedicated patients with schizophrenia and matched healthy control subjects. We here report a comparison of plasma plasmalogen levels across 20 drug-naïve patients experiencing first psychotic episodes, 20 recently unmedicated patients experiencing psychotic relapses after failing to comply with prescribed medications, and 17 matched healthy control subjects. Multiple plasma phosphatidylcholine and phosphatidylethanolamine plasmalogen levels were significantly lower in first episode patients and patients with recurrent disease compared to healthy controls. Reduced plasmalogen levels appear to be a trait evident at the onset of psychotic illness and after multiple psychotic relapses. It is implied that reductions in plasmalogen levels are not related to antipsychotic treatment but due to the illness itself. Reduced plasmalogen levels suggest impairments in membrane structure and function in patients with schizophrenia that might happen early in development. This may serve as a clue to the neurobiology of schizophrenia and should be studied as a potential biomarker for individuals at risk for schizophrenia.
Related JoVE Video
Prenatal inflammation and neurodevelopment in schizophrenia: a review of human studies.
Prog. Neuropsychopharmacol. Biol. Psychiatry
Show Abstract
Hide Abstract
A confluence of evidence supports an association between prenatal inflammation and risk of schizophrenia. Outside of studies of prenatal infections and risk of schizophrenia, other relevant human studies of prenatal inflammation and neurodevelopment in schizophrenia have not been reviewed. In this paper, we review human studies of 1) prenatal inflammation and risk of schizophrenia, 2) inflammation as a potential common mediator of several prenatal risk factors for schizophrenia other than prenatal infections, 3) prenatal inflammation and immune function, neurocognition, brain morphology, and gene expression in adult offspring with schizophrenia, and 4) gene by environment and gene by gene interactions relevant to these associations. We suggest future areas for human studies research based on existing findings.
Related JoVE Video
Taxometric analyses of paranoid and schizoid personality disorders.
Psychiatry Res
Show Abstract
Hide Abstract
There remains debate about whether personality disorders (PDs) are better conceptualized as categorical, reflecting discontinuity from normal personality; or dimensional, existing on a continuum of severity with normal personality traits. Evidence suggests that most PDs are dimensional but there is a lack of consensus about the structure of Cluster A disorders. Taxometric methods are adaptable to investigating the taxonic status of psychiatric disorders. The current study investigated the latent structure of paranoid and schizoid PDs in an epidemiological sample (N=43,093) drawn from the National Epidemiological Survey on Alcohol and Related Conditions (NESARC) using taxometric analyses. The current study used taxometric methods to analyze three indicators of paranoid PD - mistrust, resentment, and functional disturbance - and three indicators of schizoid PD - emotional detachment, social withdrawal, and functional disturbance - derived factor analytically. Overall, taxometrics supported a dimensional rather than taxonic structure for paranoid and schizoid PDs through examination of taxometric graphs and comparative curve fit indices. Dimensional models of paranoid and schizoid PDs better predicted social functioning, role-emotional, and mental health scales in the survey than categorical models. Evidence from the current study supports recent efforts to represent paranoid and schizoid PDs as well as other PDs along broad personality dimensions.
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.