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1.
J Trauma Stress ; 29(2): 149-57, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26990003

RESUMO

The primary aim of this study was to evaluate whether being treated for mental health or nonbattle physical injury during military combat deployment was associated with higher risk for postdeployment mental disorders and poorer career outcomes than seen in the general combat-deployed population. Service members treated in theater for mental health (n = 964) or noncombat injury (n = 853) were compared with randomly sampled personnel (n = 7,220) from the general deployed population on diagnosed mental disorders and early separation from service. Deployment, medical, and career information were obtained from Department of Defense archival databases. Over half of the personnel who received mental health treatment while deployed were diagnosed with 1 or more mental disorders postdeployment and/or were separated from service before completing their full-term enlistment. This was significantly higher than expected compared to the general deployed group, adjusting for demographic/military characteristics and mental health history (adjusted odds ratios [ORs] ranging 1.62 to 2.96). Frequencies of problems also were higher in the mental health-treated group than in the group treated for nonbattle physical injuries (significant adjusted ORs ranging 1.65 to 2.58). The documented higher risks for postdeployment adjustment problems suggested that especially those treated in theater by mental health providers might benefit from postdeployment risk-reduction programs.


Assuntos
Distúrbios de Guerra/terapia , Transtornos Mentais/terapia , Saúde Mental , Militares , Psicoterapia/métodos , Adulto , Distúrbios de Guerra/epidemiologia , Bases de Dados Factuais , Feminino , Humanos , Masculino , Transtornos Mentais/epidemiologia , Fatores de Risco , Estados Unidos
2.
Genome Res ; 20(6): 847-60, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20452967

RESUMO

mRNA-seq is a paradigm-shifting technology because of its superior sensitivity and dynamic range and its potential to capture transcriptomes in an agnostic fashion, i.e., independently of existing genome annotations. Implementation of the agnostic approach, however, has not yet been fully achieved. In particular, agnostic mapping of pre-mRNA splice sites has not been demonstrated. The present study pursued dual goals: (1) to advance mRNA-seq bioinformatics toward unbiased transcriptome capture and (2) to demonstrate its potential for discovery in neuroscience by applying the approach to an in vivo model of neurological disease. We have performed mRNA-seq on the L4 dorsal root ganglion (DRG) of rats with chronic neuropathic pain induced by spinal nerve ligation (SNL) of the neighboring (L5) spinal nerve. We found that 12.4% of known genes were induced and 7% were suppressed in the dysfunctional (but anatomically intact) L4 DRG 2 wk after SNL. These alterations persisted chronically (2 mo). Using a read cluster classifier with strong test characteristics (ROC area 97%), we discovered 10,464 novel exons. A new algorithm for agnostic mapping of pre-mRNA splice junctions (SJs) achieved a precision of 97%. Integration of information from all mRNA-seq read classes including SJs led to genome reannotations specifically relevant for the species used (rat), the anatomical site studied (DRG), and the neurological disease considered (pain); for example, a 64-exon coreceptor for the nociceptive transmitter substance P was identified, and 21.9% of newly discovered exons were shown to be dysregulated. Thus, mRNA-seq with agnostic analysis methods appears to provide a highly productive approach for in vivo transcriptomics in the nervous system.


Assuntos
Gânglios Espinais/metabolismo , Perfilação da Expressão Gênica , Dor/genética , Splicing de RNA , RNA Mensageiro/genética , Animais , Doença Crônica , Ratos
3.
Neuroimage ; 61(4): 1067-82, 2012 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-22542638

RESUMO

Traumatic brain injury (TBI) is a leading cause of sustained impairment in military and civilian populations. However, mild (and some moderate) TBI can be difficult to diagnose because the injuries are often not detectable on conventional MRI or CT. Injured brain tissues in TBI patients generate abnormal low-frequency magnetic activity (ALFMA, peaked at 1-4 Hz) that can be measured and localized by magnetoencephalography (MEG). We developed a new automated MEG low-frequency source imaging method and applied this method in 45 mild TBI (23 from combat-related blasts, and 22 from non-blast causes) and 10 moderate TBI patients (non-blast causes). Seventeen of the patients with mild TBI from blasts had tertiary injuries resulting from the blast. The results show our method detected abnormalities at the rates of 87% for the mild TBI group (blast-induced plus non-blast causes) and 100% for the moderate group. Among the mild TBI patients, the rates of abnormalities were 96% and 77% for the blast and non-blast TBI groups, respectively. The spatial characteristics of abnormal slow-wave generation measured by Z scores in the mild blast TBI group significantly correlated with those in non-blast mild TBI group. Among 96 cortical regions, the likelihood of abnormal slow-wave generation was less in the mild TBI patients with blast than in the mild non-blast TBI patients, suggesting possible protective effects due to the military helmet and armor. Finally, the number of cortical regions that generated abnormal slow-waves correlated significantly with the total post-concussive symptom scores in TBI patients. This study provides a foundation for using MEG low-frequency source imaging to support the clinical diagnosis of TBI.


Assuntos
Lesões Encefálicas/diagnóstico , Lesões Encefálicas/fisiopatologia , Acidentes por Quedas , Acidentes de Trânsito , Adulto , Traumatismos em Atletas/complicações , Traumatismos por Explosões/complicações , Lesões Encefálicas/etiologia , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Magnetoencefalografia , Masculino , Processamento de Sinais Assistido por Computador
4.
CNS Spectr ; 17(1): 11-5, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22790113

RESUMO

INTRODUCTION: Risk for post-traumatic stress disorder (PTSD) varies in part due to the nature of the traumatic event involved. Both injury and return from combat pose high risk of PTSD symptoms. How different injuries may predispose towards PTSD is less well understood. METHODS: A retrospective record review was conducted from 1402 service members who had returned to Naval Medical Center San Diego from Iraq or Afghanistan and who had completed the PTSD Checklist as part of their post-deployment screening. Rates of PTSD were examined in relation to mechanism of injury. RESULTS: Of those without injury, 8% met Diagnostic and Statistical Manual criteria for PTSD. Thirteen percent of those with a penetrating injury, 29% with blunt trauma, and 33% with combination injuries met criteria for PTSD. PTSD severity scores varied significantly according to type of injury. DISCUSSION: The World War I concept of "shell shock" implied that blast-related injuries were more likely to result in psychological symptoms than were other injuries. These data may support that idea. Circumstance of injury, population differences, and reporting bias could also have influenced the results. CONCLUSION: These results suggest that service members with blunt or combination injuries merit particular attention when screening for PTSD.


Assuntos
Campanha Afegã de 2001- , Lesões Encefálicas/epidemiologia , Guerra do Iraque 2003-2011 , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Adolescente , Adulto , Análise de Variância , Feminino , Hospitais Militares/estatística & dados numéricos , Humanos , Masculino , Militares/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Índices de Gravidade do Trauma , Adulto Jovem
5.
Prev Chronic Dis ; 9: E97, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22575082

RESUMO

The Marine Resiliency Study (MRS) is a prospective study of factors predictive of posttraumatic stress disorder (PTSD) among approximately 2,600 Marines in 4 battalions deployed to Iraq or Afghanistan. We describe the MRS design and predeployment participant characteristics. Starting in 2008, our research team conducted structured clinical interviews on Marine bases and collected data 4 times: at predeployment and at 1 week, 3 months, and 6 months postdeployment. Integrated with these data are medical and career histories from the Career History Archival Medical and Personnel System (CHAMPS) database. The CHAMPS database showed that 7.4% of the Marines enrolled in MRS had at least 1 mental health diagnosis. Of enrolled Marines, approximately half (51.3%) had prior deployments. We found a moderate positive relationship between deployment history and PTSD prevalence in these baseline data.


Assuntos
Militares/psicologia , Resiliência Psicológica , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Campanha Afegã de 2001- , Distúrbios de Guerra/diagnóstico , Distúrbios de Guerra/psicologia , Coleta de Dados , Bases de Dados Factuais , Emoções , Humanos , Entrevistas como Assunto , Guerra do Iraque 2003-2011 , Valor Preditivo dos Testes , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/psicologia , Inquéritos e Questionários , Ferimentos e Lesões
6.
Mil Med ; 177(4): 380-9, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22594127

RESUMO

Military personnel deployed in support of combat operations are at significantly higher risk for mental health problems. However, much of what we know about combat-related mental health comes from postdeployment assessments. This study describes the mental health of 1,336 treatment-seeking deployed U.S. military personnel and interventions recommended by military mental health providers in Iraq from January 2006 to January 2007. Cases were primarily young enlisted men, most of whom were on their first combat deployment. Marines made up the majority of the cases (60%), but there were also large numbers of Army and Navy personnel. The most common psychiatric diagnoses were anxiety disorders (31%, including 11% with posttraumatic stress disorder), followed by adjustment (27%) and mood disorders (25%, including 22% with depression). Medication was the most commonly prescribed treatment for patients with psychiatric diagnoses but was often combined with recommendations for psychotherapy/counseling and/or behavioral modifications. The findings illustrate the distribution of mental health conditions seen among treatment-seeking troops while actively serving in a combat environment and the interventions recommended for them. Further examination of postdeployment health outcomes may help to facilitate the development of more effective acute intervention strategies in theater.


Assuntos
Transtornos Mentais/diagnóstico , Transtornos Mentais/epidemiologia , Militares/psicologia , Militares/estatística & dados numéricos , Transtornos de Adaptação/diagnóstico , Transtornos de Adaptação/epidemiologia , Adolescente , Adulto , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/epidemiologia , Depressão/diagnóstico , Depressão/epidemiologia , Feminino , Humanos , Iraque , Masculino , Transtornos Mentais/terapia , Medicina Militar , Transtornos do Humor/diagnóstico , Transtornos do Humor/epidemiologia , Prevalência , Estudos Retrospectivos , Transtornos de Estresse Traumático/diagnóstico , Transtornos de Estresse Traumático/epidemiologia , Estados Unidos/epidemiologia , Guerra
7.
Psychiatr Rehabil J ; 45(2): 123-135, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34618488

RESUMO

OBJECTIVE: People with lived experience of mental illness or distress can help others recover through peer or mutual support. One way they may help others recover is by fostering generativity, which refers to one's concern for and contributions toward the betterment of others, including future generations (e.g., through caregiving, engaging in civics). Generativity may add purpose to one's life, benefit society, and improve areas which persons with lived experience feel are important for their recovery. Despite its importance, the state of knowledge on experiences and facilitators of generativity, as well as the impact that engaging in generativity has on the lives of persons engaged in peer or mutual support, is unclear. METHOD: A librarian-assisted scoping review of the literature was conducted in five steps: identifying the research question and relevance; selecting studies; charting data; and coding and summarizing the results. RESULTS: Out of 11,862 articles that were screened, only 18 met eligibility criteria. Most studies were conducted in the United States and included White/Caucasian participants. Our synthesis produced themes related to generative actions, which included helping others, changing organizations and systems, and sharing personal stories. Themes describing facilitators of generativity included individual-level and organizational-level factors. One theme reflecting the positive psychosocial impact of engaging in generativity was produced. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Findings from this study point to several knowledge gaps to be investigated in future research and can facilitate the implementation of peer support initiatives aimed at fostering generativity, which may in turn promote recovery. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Assuntos
Transtornos Mentais , Grupo Associado , Emoções , Humanos , Estados Unidos
8.
Mil Med ; 176(3): 253-60, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21456349

RESUMO

Mental health treatment of military service members places unique demands on providers as their patients experience combat stress. This study assessed levels and predictors of burnout among mental health providers (N = 97) at military facilities, using a self-administered survey of demographic and work-related measures and the Maslach Burnout Inventory. Burnout levels were comparable to studies of civilian mental health providers but were less severe than those of the Maslach Burnout Inventory normative sample. Working more hours, having more patients with personality disorders, increased patient caseloads, female gender, and being a psychiatrist were predictive of higher burnout scores. Having more confidants at work, a greater percentage of patients with traumatic brain injury, more clinical experience, and being a psychologist predicted lower burnout scores. These findings suggest that burnout levels among military providers are similar to those among civilian providers and may be alleviated by interventions targeting general institutional risk factors.


Assuntos
Esgotamento Profissional , Transtornos Mentais/terapia , Militares/psicologia , Psiquiatria Militar , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Apoio Social
9.
Mil Med ; 176(11): 1243-52, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22165651

RESUMO

Research has documented higher risks for mental health problems among service members deployed to war zones, yet a research limitation has been that assessment has generally occurred often years after combat exposure. The Operational Stress Control and Readiness program integrated mental health practitioners with 1st Marine Division units serving in Iraq. This team documented mental health visits between January 2006 and January 2007 and developed the Theater Mental Health Encounter Database (TMHED). This report describes the TMHED study design, measures, and cases. Of 1336 patients (3180 patient visits), 10% were women, 75% were high school educated, 55% were mid-paygrade enlisted, and 63% were on their first combat deployment. Compared with the overall deployed population, patient percentages included higher percentages of Marines and Navy personnel but lower percentages of Army and Air Force personnel, more junior enlisted but fewer officers, and fewer college graduates. TMHED provides an unprecedented opportunity to study early psychiatric intervention in a combat zone and prospectively examines postdeployment health and career outcomes.


Assuntos
Documentação/métodos , Guerra do Iraque 2003-2011 , Prontuários Médicos , Militares/psicologia , Psiquiatria Militar/organização & administração , Feminino , Humanos , Masculino , Serviços de Saúde Mental/organização & administração , Projetos de Pesquisa
10.
Schizophr Res ; 228: 74-82, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33434737

RESUMO

BACKGROUND: Suicide is a leading cause of death in persons with schizophrenia and other serious mental illnesses (SMI), however, little is known about the characteristics and circumstances of suicide decedents with SMI in the US compared to those with other or no known mental illness. METHODS: This study was a retrospective analysis of suicide deaths in individuals aged ≥18 years from the National Violent Death Reporting System, 2003-2017. Odds ratios compared sociodemographic and clinical characteristics, cause of death, precipitating circumstances, and post-mortem toxicology results. All analyses were stratified by gender. RESULTS: Of the 174,001 suicide decedents, 8.7% had a known SMI, 33.0% had other mental disorders, and 58.2% had no known mental illness. Relative to persons with other mental disorders, SMI decedents were younger and more likely to have previous suicide attempts and co-occurring drug use. Problems with intimate partners, poor physical health, and recent institutional release were the most common precipitating circumstances for SMI decedents. Firearms were the most common suicide method for males with SMI. Although 67.0% male and 76.0% of female SMI decedents were currently in treatment, toxicology results suggest many were not taking antipsychotic or antidepressant medications at the time of death. CONCLUSIONS: Persons with SMI are over-represented in suicide deaths. Efforts to improve treatment of co-occurring substance use disorders, continuity of care following hospitalization, medication adherence, and to reduce access to firearms are important suicide prevention strategies.


Assuntos
Transtornos Mentais , Vigilância da População , Adolescente , Adulto , Distribuição por Idade , Causas de Morte , Feminino , Humanos , Masculino , Transtornos Mentais/epidemiologia , Estudos Retrospectivos , Distribuição por Sexo , Estados Unidos/epidemiologia
11.
F1000Res ; 10: 80, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35847383

RESUMO

Next Generation Sequencing technologies significantly impact the field of Antimicrobial Resistance (AMR) detection and monitoring, with immediate uses in diagnosis and risk assessment. For this application and in general, considerable challenges remain in demonstrating sufficient trust to act upon the meaningful information produced from raw data, partly because of the reliance on bioinformatics pipelines, which can produce different results and therefore lead to different interpretations. With the constant evolution of the field, it is difficult to identify, harmonise and recommend specific methods for large-scale implementations over time. In this article, we propose to address this challenge through establishing a transparent, performance-based, evaluation approach to provide flexibility in the bioinformatics tools of choice, while demonstrating proficiency in meeting common performance standards. The approach is two-fold: first, a community-driven effort to establish and maintain "live" (dynamic) benchmarking platforms to provide relevant performance metrics, based on different use-cases, that would evolve together with the AMR field; second, agreed and defined datasets to allow the pipelines' implementation, validation, and quality-control over time. Following previous discussions on the main challenges linked to this approach, we provide concrete recommendations and future steps, related to different aspects of the design of benchmarks, such as the selection and the characteristics of the datasets (quality, choice of pathogens and resistances, etc.), the evaluation criteria of the pipelines, and the way these resources should be deployed in the community.


Assuntos
Benchmarking , Sequenciamento de Nucleotídeos em Larga Escala , Antibacterianos/farmacologia , Biologia Computacional/métodos , Farmacorresistência Bacteriana/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos
12.
F1000Res ; 72018.
Artigo em Inglês | MEDLINE | ID: mdl-30026930

RESUMO

Next-Generation Sequencing (NGS) technologies are expected to play a crucial role in the surveillance of infectious diseases, with their unprecedented capabilities for the characterisation of genetic information underlying the virulence and antimicrobial resistance (AMR) properties of microorganisms.  In the implementation of any novel technology for regulatory purposes, important considerations such as harmonisation, validation and quality assurance need to be addressed.  NGS technologies pose unique challenges in these regards, in part due to their reliance on bioinformatics for the processing and proper interpretation of the data produced.  Well-designed benchmark resources are thus needed to evaluate, validate and ensure continued quality control over the bioinformatics component of the process.  This concept was explored as part of a workshop on "Next-generation sequencing technologies and antimicrobial resistance" held October 4-5 2017.   Challenges involved in the development of such a benchmark resource, with a specific focus on identifying the molecular determinants of AMR, were identified. For each of the challenges, sets of unsolved questions that will need to be tackled for them to be properly addressed were compiled. These take into consideration the requirement for monitoring of AMR bacteria in humans, animals, food and the environment, which is aligned with the principles of a "One Health" approach.


Assuntos
Antibacterianos/farmacologia , Biologia Computacional/métodos , Farmacorresistência Bacteriana/genética , Sequenciamento de Nucleotídeos em Larga Escala , Benchmarking
13.
Mil Med ; 171(12): 1239-42, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17256692

RESUMO

It is a popularly held belief that psychiatric behavior worsens during a full moon. Research in this area has yielded mixed results. Records from Naval Medical Center San Diego for 1993-2001 were examined to see whether there were higher rates of psychiatric admission associated with particular phases of the moon. Records from 8,473 admissions revealed that there were no more admission on days with a full moon, a new moon, any quarter of the moon, a waxing moon, or a waning moon. This held true for psychiatric patients as a whole, as well as for individuals with particular diagnoses, such as those with a mood disorder or psychotic disorder. Records from 1,909 emergency psychiatric evaluations that occurred between 2002 and 2003 were also examined to see whether a higher percentage of patients might present, but not require hospitalization, during a particular phase of the moon. Once again, no significant effect was found. In summary, lunar phase was not associated in any significant way with psychiatric admissions or emergency presentation.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Serviços de Emergência Psiquiátrica/estatística & dados numéricos , Transtornos Mentais/epidemiologia , Militares/psicologia , Lua , Admissão do Paciente/estatística & dados numéricos , Periodicidade , California/epidemiologia , Folclore , Humanos , Transtornos Mentais/diagnóstico , Militares/estatística & dados numéricos , Psiquiatria Militar , Projetos Piloto , Fatores de Tempo
14.
Sci Rep ; 6: 33866, 2016 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-27649782

RESUMO

Lateral variations along the Himalayan arc are suggested by an increasing number of studies and carry important information about the orogen's segmentation. Here we compile the hitherto most complete land gravity dataset in the region which enables the currently highest resolution plausible analysis. To study lateral variations in collisional structure we compute arc-parallel gravity anomalies (APaGA) by subtracting the average arc-perpendicular profile from our dataset; we compute likewise for topography (APaTA). We find no direct correlation between APaGA, APaTA and background seismicity, as suggested in oceanic subduction context. In the Himalayas APaTA mainly reflect relief and erosional effects, whereas APaGA reflect the deep structure of the orogen with clear lateral boundaries. Four segments are outlined and have disparate flexural geometry: NE India, Bhutan, Nepal &India until Dehradun, and NW India. The segment boundaries in the India plate are related to inherited structures, and the boundaries of the Shillong block are highlighted by seismic activity. We find that large earthquakes of the past millennium do not propagate across the segment boundaries defined by APaGA, therefore these seem to set limits for potential rupture of megathrust earthquakes.

15.
Mil Med ; 170(3): 219-22, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15828698

RESUMO

Admission data from 6366 patients on the psychiatry service at Naval Medical Center San Diego were used to form a linear regression model to examine variables that might influence length of stay. Information was available on active duty status, primary diagnosis, age, gender, and marital status. Active duty service, older age, single marital status, and a primary diagnosis of a psychotic or mood disorder were all significantly associated with longer hospital stays. Primary diagnosis of an adjustment or personality disorder was associated with a shorter stay. Taking into account these variables, lengths of stay for active duty personnel averaged 4.00 +/- 0.39 days longer than for equivalent civilian admissions. Although military personnel are generally thought of as a healthy population, psychiatric hospital stays were found to be longer in service members than in their civilian counterparts. Financial repercussions and possible reasons for this are discussed.


Assuntos
Hospitais Militares/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Psiquiatria Militar/estatística & dados numéricos , Unidade Hospitalar de Psiquiatria/estatística & dados numéricos , Adolescente , Adulto , Idoso , California , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Militares/psicologia , Análise de Regressão , Estados Unidos , Revisão da Utilização de Recursos de Saúde
16.
Psychiatr Serv ; 62(1): 15-21, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21209294

RESUMO

OBJECTIVE: This purpose of this study was to determine the incidence and types of preexisting mental disorders among military personnel who received mental health services in an Iraqi war zone. METHODS: The study examined psychiatric histories of 1,078 American military personnel (Marines, 65%; Army, 23%; Navy, 11%; and Air Force, <1%) deployed to Iraq and seen by in-theater mental health providers between January 2006 and February 2007. RESULTS: Among the 1,078 patients, the most frequent in-theater diagnoses were anxiety (24%), adjustment (23%), and mood (19%) disorders. Twenty-nine percent of the sample (N=308) had a psychiatric diagnosis in their medical records before their first encounter with mental health services in Iraq (Navy patients, 42%; Army patients, 39%; and Marine Corps patients, 23%). The mean time between last predeployment diagnosis and first in-theater mental health encounter was 21 months. For patients with a prior diagnosis, the highest rate of relapse (receipt of the same diagnosis in theater) was for attention-deficit hyperactivity disorder (57%), followed by anxiety disorders (44%)--especially posttraumatic stress disorder (PTSD) (55%)--mood disorders (38%), and adjustment disorders (32%). CONCLUSIONS: A significant proportion of military personnel who experienced mental health problems in a combat zone had preexisting psychiatric conditions. Because more than half of predeployment diagnoses were received in the nine months before the in-theater mental health encounter, further study may be advisable to determine whether a time-based algorithm for deployability is needed, particularly for PTSD, for which a high rate of repeat diagnosis in theater was found.


Assuntos
Transtornos Mentais/epidemiologia , Militares/psicologia , Adulto , Comorbidade , Feminino , Humanos , Incidência , Guerra do Iraque 2003-2011 , Masculino , Recidiva , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Estados Unidos/epidemiologia
18.
PLoS One ; 5(1): e8956, 2010 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-20126463

RESUMO

Brain serotonin (5-HT) neurotransmission plays a key role in the regulation of mood and has been implicated in a variety of neuropsychiatric conditions. Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the biosynthesis of 5-HT. Recently, we discovered a second TPH isoform (TPH2) in vertebrates, including man, which is predominantly expressed in brain, while the previously known TPH isoform (TPH1) is primarly a non-neuronal enzyme. Overwhelming evidence now points to TPH2 as a candidate gene for 5-HT-related psychiatric disorders. To assess the role of TPH2 gene variability in the etiology of psychiatric diseases we performed cDNA sequence analysis of TPH2 transcripts from human post mortem amygdala samples obtained from individuals with psychiatric disorders (drug abuse, schizophrenia, suicide) and controls. Here we show that TPH2 exists in two alternatively spliced variants in the coding region, denoted TPH2a and TPH2b. Moreover, we found evidence that the pre-mRNAs of both splice variants are dynamically RNA-edited in a mutually exclusive manner. Kinetic studies with cell lines expressing recombinant TPH2 variants revealed a higher activity of the novel TPH2B protein compared with the previously known TPH2A, whereas RNA editing was shown to inhibit the enzymatic activity of both TPH2 splice variants. Therefore, our results strongly suggest a complex fine-tuning of central nervous system 5-HT biosynthesis by TPH2 alternative splicing and RNA editing. Finally, we present molecular and large-scale linkage data evidencing that deregulated alternative splicing and RNA editing is involved in the etiology of psychiatric diseases, such as suicidal behaviour.


Assuntos
Processamento Alternativo , Edição de RNA , Triptofano Hidroxilase/genética , Humanos
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