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1.
Occup Med (Lond) ; 70(3): 162-168, 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32040153

RESUMO

BACKGROUND: Pre-employment psychological screening to detect psychological vulnerability is common amongst emergency service organizations worldwide, yet the evidence for its ability to predict poor mental health outcomes is limited with published studies looking at post-recruitment research data rather than data collected by the organizations themselves. AIMS: The present study sought to investigate the ability of pre-employment screening to predict later psychological injury-related absenteeism amongst police officers. METHODS: A nested case-control study using prospective data was conducted. One hundred and fifty police officers with a liability-accepted psychological injury were matched to a control group of 150 psychologically healthy officers. Conditional logistic regression was used to examine associations between Minnesota Multiphasic Personality Inventory-2 (MMPI-2) scales measuring factors research has shown to predict psychological injury (Neuroticism, Psychoticism, Introversion, Disconstraint and Aggressiveness) and psychopathology (Depression, Anxiety and post-traumatic stress disorder [PTSD]) with subsequent psychological injury. RESULTS: Contrary to expectations, we were unable to demonstrate any association between validated pre-employment measures of personality and psychopathology with mental health outcomes amongst newly recruited police officers over a 7-year follow-up. CONCLUSIONS: Other measures may be better able to predict future mental health problems in police recruits.


Assuntos
Transtornos Mentais/psicologia , Doenças Profissionais/psicologia , Polícia/psicologia , Austrália , Estudos de Casos e Controles , Emprego/psicologia , Feminino , Humanos , MMPI , Masculino , Transtornos Mentais/diagnóstico , Determinação da Personalidade , Estudos Prospectivos , Licença Médica/estatística & dados numéricos
2.
Psychol Med ; 47(1): 115-126, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27670088

RESUMO

BACKGROUND: Although perceived social support is thought to be a strong predictor of psychological outcomes following trauma exposure, the temporal relationship between perceived positive and negative social support and post-traumatic stress disorder (PTSD) symptoms has not been empirically established. This study investigated the temporal sequencing of perceived positive social support, perceived negative social support, and PTSD symptoms in the 6 years following trauma exposure among survivors of traumatic injury. METHOD: Participants were 1132 trauma survivors initially assessed upon admission to one of four Level 1 trauma hospitals in Australia after experiencing a traumatic injury. Participants were followed up at 3 months, 12 months, 24 months, and 6 years after the traumatic event. RESULTS: Latent difference score analyses revealed that greater severity of PTSD symptoms predicted subsequent increases in perceived negative social support at each time-point. Greater severity of PTSD symptoms predicted subsequent decreases in perceived positive social support between 3 and 12 months. High levels of perceived positive or negative social support did not predict subsequent changes in PTSD symptoms at any time-point. CONCLUSIONS: Results highlight the impact of PTSD symptoms on subsequent perceived social support, regardless of the type of support provided. The finding that perceived social support does not influence subsequent PTSD symptoms is novel, and indicates that the relationship between PTSD and perceived social support may be unidirectional.


Assuntos
Apoio Social , Transtornos de Estresse Pós-Traumáticos/psicologia , Sobreviventes/psicologia , Ferimentos e Lesões/psicologia , Adulto , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade
3.
Psychol Med ; 47(11): 2028-2035, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28535839

RESUMO

BACKGROUND: Prolonged separation from parental support is a risk factor for psychopathology. This study assessed the impact of brief separation from parents during childhood trauma on adult attachment tendencies and post-traumatic stress. METHOD: Children (n = 806) exposed to a major Australian bushfire disaster in 1983 and matched controls (n = 725) were assessed in the aftermath of the fires (mean age 7-8 years) via parent reports of trauma exposure and separation from parents during the fires. Participants (n = 500) were subsequently assessed 28 years after initial assessment on the Experiences in Close Relationships scale to assess attachment security, and post-traumatic stress disorder (PTSD) was assessed using the PTSD checklist. RESULTS: Being separated from parents was significantly related to having an avoidant attachment style as an adult (B = -3.69, s.e. = 1.48, ß = -0.23, p = 0.013). Avoidant attachment was associated with re-experiencing (B = 0.03, s.e. = 0.01, ß = 0.31, p = 0.045), avoidance (B = 0.03, s.e. = 0.01, ß = 0.30, p = 0.001) and numbing (B = 0.03, s.e. = 0.01, ß = 0.30, p < 0.001) symptoms. Anxious attachment was associated with re-experiencing (B = 0.03, s.e. = 0.01, ß = 0.18, p = 0.001), numbing (B = 0.03, ß = 0.30, s.e. = 0.01, p < 0.001) and arousal (B = 0.04, s.e. = 0.01, ß = 0.43, p < 0.001) symptoms. CONCLUSIONS: These findings demonstrate that brief separation from attachments during childhood trauma can have long-lasting effects on one's attachment security, and that this can be associated with adult post-traumatic psychopathology.


Assuntos
Adultos Sobreviventes de Eventos Adversos na Infância/psicologia , Apego ao Objeto , Relações Pais-Filho , Transtornos de Estresse Pós-Traumáticos/etiologia , Incêndios Florestais , Adulto , Adultos Sobreviventes de Eventos Adversos na Infância/estatística & dados numéricos , Austrália/epidemiologia , Criança , Desastres/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Masculino , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Incêndios Florestais/estatística & dados numéricos
4.
Psychol Med ; 43(10): 2153-60, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23406821

RESUMO

BACKGROUND: Many patients do not adhere to or benefit from cognitive behaviour therapy (CBT) for post-traumatic stress disorder (PTSD). This randomized controlled trial evaluates the extent to which preparing patients with emotion regulation skills prior to CBT enhances treatment outcome. METHOD: A total of 70 adult civilian patients with PTSD were randomized to 12 sessions of either supportive counselling followed by CBT (Support/CBT) or emotion regulation training followed by CBT (Skills/CBT). RESULTS: Skills/CBT resulted in fewer treatment drop-outs, less PTSD and anxiety, and fewer negative appraisals at 6 months follow-up than Support/CBT. Between-condition effect size was moderate for PTSD severity (0.43, 95% confidence interval x0.04 to 0.90). More Skills/CBT (31%) patients achieved high end-state functioning at follow-up than patients in Support/CBT (12%) [Χ2(n=70)=3.67, p<0.05]. CONCLUSIONS: This evidence suggests that response to CBT may be enhanced in PTSD patients by preparing them with emotion regulation skills. High attrition of participants during the study limits conclusions from this study.


Assuntos
Psicoterapia/métodos , Transtornos de Estresse Pós-Traumáticos/terapia , Adaptação Psicológica/fisiologia , Adulto , Terapia Cognitivo-Comportamental/instrumentação , Terapia Cognitivo-Comportamental/métodos , Aconselhamento/métodos , Emoções/fisiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Desistentes do Tratamento/psicologia , Psicoterapia/instrumentação , Índice de Gravidade de Doença , Resultado do Tratamento
5.
Psychol Med ; 42(8): 1695-703, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22166813

RESUMO

BACKGROUND: Few studies have focused on post-traumatic stress disorder (PTSD) remission in the population, none have modelled remission beyond age 54 years and none have explored in detail the correlates of remission from PTSD. This study examined trauma experience, symptom severity, co-morbidity, service use and time to PTSD remission in a large population sample. METHOD: Data came from respondents (n=8841) of the 2007 Australian National Survey of Mental Health and Wellbeing (NSMHWB). A modified version of the World Health Organization's World Mental Health Composite International Diagnostic Interview (WMH-CIDI) was used to determine the presence and age of onset of DSM-IV PTSD and other mental and substance use disorders, type, age, and number of lifetime traumas, severity of re-experiencing, avoidance and hypervigilance symptoms and presence and timing of service use. RESULTS: Projected lifetime remission rate was 92% and median time to remission was 14 years. Those who experienced childhood trauma, interpersonal violence, severe symptoms or a secondary anxiety or affective disorder were less likely to remit from PTSD and reported longer median times to remission compared to those with other trauma experiences, less severe symptoms or no co-morbidity. CONCLUSIONS: Although most people in the population with PTSD eventually remit, a significant minority report symptoms decades after onset. Those who experience childhood trauma or interpersonal violence should be a high priority for intervention.


Assuntos
Acontecimentos que Mudam a Vida , Transtornos Mentais/epidemiologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Adolescente , Adulto , Idade de Início , Idoso , Austrália/epidemiologia , Criança , Comorbidade , Manual Diagnóstico e Estatístico de Transtornos Mentais , Métodos Epidemiológicos , Feminino , Humanos , Entrevista Psicológica , Masculino , Serviços de Saúde Mental/estatística & dados numéricos , Pessoa de Meia-Idade , Remissão Espontânea , Fatores de Tempo , Violência , Adulto Jovem
6.
Psychol Med ; 41(12): 2573-80, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21672298

RESUMO

BACKGROUND: Fear circuitry disorders purportedly include post-traumatic stress disorder (PTSD), panic disorder, agoraphobia, social phobia and specific phobia. It is proposed that these disorders represent a cluster of anxiety disorders triggered by stressful events and lead to fear conditioning. Elevated heart rate (HR) at the time of an aversive event may reflect strength of the unconditioned response, which may contribute to fear circuitry disorders. METHOD: This prospective cohort study assessed HR within 48 h of hospital admission in 602 traumatically injured patients, who were assessed during hospital admission and within 1 month of trauma exposure for lifetime psychiatric diagnosis. At 3 months after the initial assessment, 526 patients (87%) were reassessed for PTSD, major depressive disorder, panic disorder, agoraphobia, social phobia, obsessive compulsive disorder and generalized anxiety disorder. RESULTS: At the 3-month assessment there were 77 (15%) new cases of fear circuitry disorder and 87 new cases of non-fear circuitry disorder (17%). After controlling for gender, age, type of injury and injury severity, patients with elevated HR (defined as ≥96 beats per min) at the time of injury were more likely to develop PTSD [odds ratio (OR) 5.78, 95% confidence interval (CI) 2.32-14.43], panic disorder (OR 3.46, 95% CI 1.16-10.34), agoraphobia (OR 3.90, 95% CI 1.76-8.61) and social phobia (OR 3.98, 95% CI 1.42-11.14). Elevated HR also predicted new fear circuitry disorders that were not co-morbid with a non-fear circuitry disorder (OR 7.28, 95% CI 2.14-24.79). CONCLUSIONS: These data provide tentative evidence of a common mechanism underpinning the onset of fear circuitry disorders.


Assuntos
Transtornos de Ansiedade/etiologia , Medo/fisiologia , Frequência Cardíaca/fisiologia , Ferimentos e Lesões/psicologia , Adulto , Agorafobia/etiologia , Agorafobia/fisiopatologia , Transtornos de Ansiedade/fisiopatologia , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Transtorno de Pânico/etiologia , Transtorno de Pânico/fisiopatologia , Transtornos Fóbicos/etiologia , Transtornos Fóbicos/fisiopatologia , Estudos Prospectivos , Transtornos de Estresse Pós-Traumáticos/etiologia , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Ferimentos e Lesões/fisiopatologia
7.
J Exp Med ; 191(7): 1177-86, 2000 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-10748235

RESUMO

The major histocompatibility complex (MHC) class II-associated invariant chain (Ii) regulates intracellular trafficking and peptide loading of MHC class II molecules. Such loading occurs after endosomal degradation of the invariant chain to a approximately 3-kD peptide termed CLIP (class II-associated invariant chain peptide). Cathepsins L and S have both been implicated in degradation of Ii to CLIP in thymus and peripheral lymphoid organs, respectively. However, macrophages from mice deficient in both cathepsins S and L can process Ii and load peptides onto MHC class II dimers normally. Both processes are blocked by a cysteine protease inhibitor, indicating the involvement of an additional Ii-processing enzyme(s). Comparison of cysteine proteases expressed by macrophages with those found in splenocytes and dendritic cells revealed two enzymes expressed exclusively in macrophages, cathepsins Z and F. Recombinant cathepsin Z did not generate CLIP from Ii-MHC class II complexes, whereas cathepsin F was as efficient as cathepsin S in CLIP generation. Inhibition of cathepsin F activity and MHC class II peptide loading by macrophages exhibited similar specificity and activity profiles. These experiments show that cathepsin F, in a subset of antigen presenting cells (APCs), can efficiently degrade Ii. Different APCs can thus use distinct proteases to mediate MHC class II maturation and peptide loading.


Assuntos
Apresentação de Antígeno/imunologia , Antígenos de Diferenciação de Linfócitos B/imunologia , Catepsinas/imunologia , Endopeptidases , Antígenos de Histocompatibilidade Classe II/imunologia , Macrófagos Alveolares/imunologia , Animais , Catepsina F , Catepsina L , Catepsinas/antagonistas & inibidores , Catepsinas/genética , Cricetinae , Cisteína Endopeptidases , Inibidores de Cisteína Proteinase/farmacologia , Dipeptídeos/farmacologia , Expressão Gênica , Humanos , Imunoglobulina E/imunologia , Leucina/análogos & derivados , Leucina/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Peptídeos/imunologia , Sulfonas/farmacologia
8.
Psychol Med ; 40(7): 1215-23, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19811699

RESUMO

BACKGROUND: Pain and post-traumatic stress disorder (PTSD) are frequently co-morbid in the aftermath of a traumatic event. Although several models attempt to explain the relationship between these two disorders, the mechanisms underlying the relationship remain unclear. The aim of this study was to investigate the relationship between each PTSD symptom cluster and pain over the course of post-traumatic adjustment. METHOD: In a longitudinal study, injury patients (n=824) were assessed within 1 week post-injury, and then at 3 and 12 months. Pain was measured using a 100-mm Visual Analogue Scale (VAS). PTSD symptoms were assessed using the Clinician-Administered PTSD Scale (CAPS). Structural equation modelling (SEM) was used to identify causal relationships between pain and PTSD. RESULTS: In a saturated model we found that the relationship between acute pain and 12-month pain was mediated by arousal symptoms at 3 months. We also found that the relationship between baseline arousal and re-experiencing symptoms, and later 12-month arousal and re-experiencing symptoms, was mediated by 3-month pain levels. The final model showed a good fit [chi2=16.97, df=12, p>0.05, Comparative Fit Index (CFI)=0.999, root mean square error of approximation (RMSEA)=0.022]. CONCLUSIONS: These findings provide evidence of mutual maintenance between pain and PTSD.


Assuntos
Dor/epidemiologia , Dor/psicologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Adolescente , Adulto , Idoso , Nível de Alerta/fisiologia , Doença Crônica , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/diagnóstico , Medição da Dor , Índice de Gravidade de Doença , Inquéritos e Questionários , Adulto Jovem
10.
Mol Psychiatry ; 14(7): 681-95, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19153574

RESUMO

Individual risk markers for depression and anxiety disorders have been identified but the explicit pathways that link genes and environment to these markers remain unknown. Here we examined the explicit interactions between the brain-derived neurotrophic factor (BDNF) Val66Met gene and early life stress (ELS) exposure in brain (amygdala-hippocampal-prefrontal gray matter volume), body (heart rate), temperament and cognition in 374 healthy European volunteers assessed for depression and anxiety symptoms. Brain imaging data were based on a subset of 89 participants. Multiple regression analysis revealed main effects of ELS for body arousal (resting heart rate, P=0.005) and symptoms (depression and anxiety, P<0.001) in the absence of main effects for BDNF. In addition, significant BDNF-ELS interactions indicated that BDNF Met carriers exposed to greater ELS have smaller hippocampal and amygdala volumes (P=0.013), heart rate elevations (P=0.0002) and a decline in working memory (P=0.022). Structural equation path modeling was used to determine if this interaction predicts anxiety and depression by mediating effects on the brain, body and cognitive measures. The combination of Met carrier status and exposure to ELS predicted reduced gray matter in hippocampus (P<0.001), and associated lateral prefrontal cortex (P<0.001) and, in turn, higher depression (P=0.005). Higher depression was associated with poorer working memory (P=0.005), and slowed response speed. The BDNF Met-ELS interaction also predicted elevated neuroticism and higher depression and anxiety by elevations in body arousal (P<0.001). In contrast, the combination of BDNF V/V genotype and ELS predicted increases in gray matter of the amygdala (P=0.003) and associated medial prefrontal cortex (P<0.001), which in turn predicted startle-elicited heart rate variability (P=0.026) and higher anxiety (P=0.026). Higher anxiety was linked to verbal memory, and to impulsivity. These effects were specific to the BDNF gene and were not evident for the related 5HTT-LPR polymorphism. Overall, these findings are consistent with the correlation of depression and anxiety, yet suggest that partially differentiated gene-brain cognition pathways to these syndromes can be identified, even in a nonclinical sample. Such findings may aid establishing an evidence base for more tailored intervention strategies.


Assuntos
Ansiedade , Nível de Alerta/fisiologia , Fator Neurotrófico Derivado do Encéfalo/genética , Encéfalo/patologia , Depressão , Metionina/genética , Polimorfismo Genético/genética , Valina/genética , Adulto , Ansiedade/etiologia , Ansiedade/genética , Ansiedade/patologia , Mapeamento Encefálico , Depressão/etiologia , Depressão/genética , Depressão/patologia , Feminino , Frequência Cardíaca/genética , Humanos , Imageamento por Ressonância Magnética , Masculino , Memória/fisiologia , Pessoa de Meia-Idade , Modelos Biológicos , Vias Neurais/patologia , Vias Neurais/fisiopatologia , Testes Neuropsicológicos , Análise de Regressão , Estresse Psicológico/complicações , Adulto Jovem
11.
J Cell Biol ; 147(4): 775-90, 1999 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-10562280

RESUMO

Before a class II molecule can be loaded with antigenic material and reach the surface to engage CD4+ T cells, its chaperone, the class II-associated invariant chain (Ii), is degraded in a stepwise fashion by proteases in endocytic compartments. We have dissected the role of cathepsin S (CatS) in the trafficking and maturation of class II molecules by combining the use of dendritic cells (DC) from CatS(-/-) mice with a new active site-directed probe for direct visualization of active CatS. Our data demonstrate that CatS is active along the entire endocytic route, and that cleavage of the lysosomal sorting signal of Ii by CatS can occur there in mature DC. Genetic disruption of CatS dramatically reduces the flow of class II molecules to the cell surface. In CatS(-/-) DC, the bulk of major histocompatibility complex (MHC) class II molecules is retained in late endocytic compartments, although paradoxically, surface expression of class II is largely unaffected. The greatly diminished but continuous flow of class II molecules to the cell surface, in conjunction with their long half-life, can account for the latter observation. We conclude that in DC, CatS is a major determinant in the regulation of intracellular trafficking of MHC class II molecules.


Assuntos
Catepsinas/metabolismo , Células Dendríticas/imunologia , Antígenos de Histocompatibilidade Classe II/genética , Animais , Catepsinas/deficiência , Catepsinas/genética , Células Cultivadas , Células Dendríticas/enzimologia , Células Dendríticas/ultraestrutura , Endocitose , Citometria de Fluxo , Genes MHC Classe I , Antígenos de Histocompatibilidade Classe II/análise , Antígenos de Histocompatibilidade Classe II/biossíntese , Cinética , Ligantes , Proteínas de Membrana/farmacologia , Proteínas de Membrana/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Baço/imunologia , Frações Subcelulares/imunologia
12.
Epidemiol Psychiatr Sci ; 29: e44, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31423962

RESUMO

AIMS: Despite the frequency that refugees suffer bereavement, there is a dearth of research into the prevalence and predictors of problematic grief reactions in refugees. To address this gap, this study reports a nationally representative population-based study of refugees to determine the prevalence of probable prolonged grief disorder (PGD) and its associated problems. METHODS: This study recruited participants from the Building a New Life in Australia (BNLA) prospective cohort study of refugees admitted to Australia between October 2013 and February 2014. The current data were collected in 2015-2016, and comprised 1767 adults, as well as 411 children of the adult respondents. Adult refugees were assessed for trauma history, post-migration difficulties, probable PGD, post-traumatic stress disorder (PTSD) and mental illness. Children were administered the Strengths and Difficulties Questionnaire. RESULTS: In this cohort, 38.1% of refugees reported bereavement, of whom 15.8% reported probable PGD; this represents 6.0% of the entire cohort. Probable PGD was associated with a greater likelihood of mental illness, probable PTSD, severe mental illness, currently unemployed and reported disability. Children of refugees with probable PGD reported more psychological difficulties than those whose parents did not have probable PGD. Probable PGD was also associated with the history of imprisonment, torture and separation from family. Only 56.3% of refugees with probable PGD had received psychological assistance. CONCLUSIONS: Bereavement and probable PGD appear highly prevalent in refugees, and PGD seems to be associated with disability in the refugees and psychological problems in their children. The low rate of access to mental health assistance for these refugees highlights that there is a need to address this issue in refugee populations.


Assuntos
Transtornos de Ansiedade/epidemiologia , Transtorno Depressivo/epidemiologia , Pesar , Refugiados/estatística & dados numéricos , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Adolescente , Adulto , África/etnologia , Ásia/etnologia , Austrália/epidemiologia , Luto , Estudos de Coortes , Feminino , Humanos , Masculino , Transtornos Mentais , Pessoa de Meia-Idade , Estudos Prospectivos , Refugiados/psicologia , Fatores de Risco , Adulto Jovem
13.
Epidemiol Psychiatr Sci ; 28(1): 77-87, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28689511

RESUMO

AIMS: The aim of this feasibility trial was to evaluate the feasibility and acceptability of the locally adapted Group Problem Management Plus (PM+) intervention for women in the conflict affected settings in Swat, Pakistan. METHODS: This mixed-methods study incorporated a quantitative component consisting of a two arm cluster randomised controlled feasibility trial, and qualitative evaluation of the acceptability of the Group PM+ to a range of stakeholder groups. For the quantitative component, on average from each of the 20 Lady Health Workers (LHWs) catchment area (20 clusters), six women were screened and recruited for the trial with score of >2 on the General Health Questionnaire and score of >16 on the WHO Disability Assessment Schedule. These LHW clusters were randomised on a 1 : 1 allocation ratio using a computer-based software through a simple randomisation method to the Group PM+ intervention or Enhanced Usual Care. The Group PM+ intervention consisted of five weekly sessions of 2 h duration delivered by local non-specialist females under supervision. The primary outcome was individual psychological distress, measured by levels of anxiety and depression on the Hospital Anxiety and Depression Scale at 7th week after baseline. Secondary outcomes include symptoms of depression, post-traumatic stress disorder (PTSD), general psychological profile, levels of functioning and generalised psychological distress. Intervention acceptability was explored through in-depth interviews. RESULTS: The results show that lay-helpers with no prior mental health experience can be trained to achieve the desired competency to successfully deliver the intervention in community settings under supervision. There was a good intervention uptake, with Group PM+ considered useful by participants, their families and lay-helpers. The outcome evaluation, which was not based on a large enough study to identify statistically significant results, indicated statistically significant improvements in depression, anxiety, general psychological profile and functioning. The PTSD symptoms and depressive disorder scores showed a trend in favour of the intervention. CONCLUSION: This trial showed robust acceptance in the local settings with delivery by non-specialists under supervision by local trained females. The trial paves the way for further adaptation and exploration of the outcomes through larger-scale implementation and definitive randomised controlled trials in the local settings.


Assuntos
Ansiedade/diagnóstico , Ansiedade/psicologia , Conflitos Armados/psicologia , Serviços Comunitários de Saúde Mental/organização & administração , Depressão/diagnóstico , Depressão/psicologia , Aceitação pelo Paciente de Cuidados de Saúde , Qualidade de Vida/psicologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Adulto , Ansiedade/etnologia , Atenção à Saúde , Depressão/etnologia , Estudos de Viabilidade , Feminino , Humanos , Entrevistas como Assunto , Pessoa de Meia-Idade , Paquistão/epidemiologia , Aceitação pelo Paciente de Cuidados de Saúde/etnologia , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Psicoterapia de Grupo , Pesquisa Qualitativa , População Rural , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/etnologia , Estresse Psicológico
14.
Cancer Biol Ther ; 20(2): 169-182, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30183475

RESUMO

Targeting the early steps of the glycolysis pathway in cancers is a well-established therapeutic strategy; however, the doses required to elicit a therapeutic effect on the cancer can be toxic to the patient. Consequently, numerous preclinical and clinical studies have combined glycolytic blockade with other therapies. However, most of these other therapies do not specifically target cancer cells, and thus adversely affect normal tissue. Here we first show that a diverse number of cancer models - spontaneous, patient-derived xenografted tumor samples, and xenografted human cancer cells - can be efficiently targeted by 2-deoxy-D-Glucose (2DG), a well-known glycolytic inhibitor. Next, we tested the cancer-cell specificity of a therapeutic compound using the MEC1 cell line, a chronic lymphocytic leukemia (CLL) cell line that expresses activation induced cytidine deaminase (AID). We show that MEC1 cells, are susceptible to 4,4'-Diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS), a specific RAD51 inhibitor. We then combine 2DG and DIDS, each at a lower dose and demonstrate that this combination is more efficacious than fludarabine, the current standard- of- care treatment for CLL. This suggests that the therapeutic blockade of glycolysis together with the therapeutic inhibition of RAD51-dependent homologous recombination can be a potentially beneficial combination for targeting AID positive cancer cells with minimal adverse effects on normal tissue. Implications: Combination therapy targeting glycolysis and specific RAD51 function shows increased efficacy as compared to standard of care treatments in leukemias.


Assuntos
Ácido 4,4'-Di-Isotiocianoestilbeno-2,2'-Dissulfônico/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Desoxiglucose/farmacologia , Neoplasias/tratamento farmacológico , Rad51 Recombinase/antagonistas & inibidores , Ácido 4,4'-Di-Isotiocianoestilbeno-2,2'-Dissulfônico/administração & dosagem , Animais , Linhagem Celular Tumoral , Desoxiglucose/administração & dosagem , Sinergismo Farmacológico , Feminino , Glicólise/efeitos dos fármacos , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Neoplasias/metabolismo , Rad51 Recombinase/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
15.
J Neurol Neurosurg Psychiatry ; 79(3): 300-6, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17702772

RESUMO

BACKGROUND: The aetiology of postconcussion syndrome (PCS) following mild traumatic brain injury (mTBI) remains controversial. Identifying acute PCS (within the first 14 days after injury) may optimise initial recovery and rehabilitation, identify those at risk and increase understanding of PCS. OBJECTIVE: To examine predictors of acute outcome by investigating the relationship between preinjury psychiatric disorder, demographic factors, injury related characteristics, neuropsychological and psychological variables and acute PCS. METHODS: Prospective study of consecutive trauma admissions to a level 1 trauma hospital. The final sample comprised 90 patients with mTBI and 85 non-brain injured trauma controls. Individuals were administered a PCS checklist, and neuropsychological and psychological measures. Multiple imputation of missing data in multivariable logistic regression and bivariate logistic regressions were used to predict acute PCS at a mean of 4.90 days after injury. RESULTS: Diagnosis of acute PCS was not specific to mTBI (mTBI 43.3%; controls 43.5%). Pain was associated with acute PCS in mTBI. The strongest effect for acute PCS was a previous affective or anxiety disorder (OR 5.76, 95% CI 2.19 to 15.0). Females were 3.33 times more likely than males to have acute PCS (95% CI 1.20 to 9.21). The effect of acute post-traumatic stress and neuropsychological function on acute PCS was relatively small. Higher IQ was associated with acute PCS. CONCLUSIONS: There is a high rate of acute PCS in both mTBI and non-brain injured trauma patients. PCS was not found to be specific to mTBI. The use of the term PCS may be misleading as it incorrectly suggests that the basis of PCS is a brain injury.


Assuntos
Lesões Encefálicas/epidemiologia , Síndrome Pós-Concussão/diagnóstico , Adolescente , Adulto , Idoso , Austrália/epidemiologia , Lesões Encefálicas/diagnóstico , Estudos de Casos e Controles , Causalidade , Comorbidade , Diagnóstico Diferencial , Feminino , Humanos , Escala de Gravidade do Ferimento , Modelos Logísticos , Masculino , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Dor/epidemiologia , Síndrome Pós-Concussão/epidemiologia , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Distribuição por Sexo , Transtornos de Estresse Pós-Traumáticos/epidemiologia
16.
Artigo em Inglês | MEDLINE | ID: mdl-30128163

RESUMO

BACKGROUND: Exposure to armed conflict and forced displacement constitute significant risks for mental health. Existing evidence-based psychological interventions have limitations for scaling-up in low-resource humanitarian settings. The WHO has developed a guided self-help intervention, Self Help Plus (SH+), which is brief, implemented by non-specialists, and designed to be delivered to people with and without specific mental disorders. This paper outlines the study protocol for an evaluation of the SH+ intervention in northern Uganda, with South Sudanese refugee women. METHODS: A two-arm, single-blind cluster-randomised controlled trial will be conducted in 14 villages in Rhino Camp refugee settlement, with at least 588 women experiencing psychological distress. Villages will be randomly assigned to receive either SH+ with enhanced usual care (EUC), or EUC alone. SH+ is a five-session guided self-help intervention delivered in workshops with audio-recorded materials and accompanying pictorial guide. The primary outcome is reduction in overall psychological distress over time, with 3 months post-treatment as the primary end-point. Secondary outcomes are self-defined psychosocial concerns, depression and post-traumatic stress disorder symptoms, hazardous alcohol use, feelings of anger, interethnic relations, psychological flexibility, functional impairment and subjective wellbeing. Psychological flexibility is a hypothesised mediator, and past trauma history and intervention attendance will be explored as potential moderators. DISCUSSION: This trial will provide important information on the effectiveness of a scalable, guided self-help intervention for improving psychological health and wellbeing among people affected by adversity. TRIAL REGISTRATION: ISRCTN50148022; registered 13/03/2017.

17.
Transl Psychiatry ; 6(10): e925, 2016 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-27754486

RESUMO

The FKBP5 polymorphism is a key regulator of the glucocorticoid system underpinning stress responsivity, and risk alleles can increase vulnerability for developing posttraumatic stress disorder. To delineate the specific role of FKBP5 risk alleles unencumbered by the confounds of psychopathology, this study investigated whether high-risk alleles of the FKBP5 polymorphism are characterized by distinctive neural activity during resting state. Thirty-seven healthy participants were selected on the basis of four SNPs in the FKBP5 gene region (rs3800373, rs9296158, rs1360780 and rs9470080) to determine participants who were carriers of the FKBP5 high- and low-risk alleles. Spatial maps, power spectra and connectivity in neural networks active during resting state were assessed with functional magnetic resonance imaging (fMRI). During resting-state fMRI, FKBP5 low-risk allele group displayed more power in the low frequency range (<0.1 Hz) than the high-risk allele group, who had significantly more power in higher frequency bins (>0.15 Hz). This difference was apparent only in a frontotemporoparietal network underpinning salience detection and emotion processing. This study provides initial evidence that the risk alleles of the FKBP5 polymorphism are associated with different resting-state activity in a frontotemporal-parietal network, and may point to mechanisms underpinning high-risk carriers' vulnerability to severe stress reactions.


Assuntos
Alelos , Lobo Frontal/fisiopatologia , Imageamento por Ressonância Magnética , Rede Nervosa/fisiopatologia , Lobo Parietal/fisiopatologia , Polimorfismo Genético/genética , Transtornos de Estresse Pós-Traumáticos/genética , Proteínas de Ligação a Tacrolimo/genética , Lobo Temporal/fisiopatologia , Nível de Alerta/genética , Nível de Alerta/fisiologia , Mapeamento Encefálico , Emoções/fisiologia , Feminino , Triagem de Portadores Genéticos , Genótipo , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Masculino , Sistema Hipófise-Suprarrenal/fisiopatologia , Risco , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Adulto Jovem
18.
Am J Psychiatry ; 157(4): 626-8, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10739425

RESUMO

OBJECTIVE: To assess the ability of acute stress disorder to predict posttraumatic stress disorder (PTSD), the relationship between acute stress disorder and PTSD over the 2 years following mild traumatic brain injury was determined. METHOD: Survivors of motor vehicle accidents who sustained mild traumatic brain injuries were assessed for acute stress disorder within 1 month of the trauma (N=79) and for PTSD at 6 months (N=63) and 2 years (N=50) posttrauma. RESULTS: Acute stress disorder was diagnosed in 14% of the patients. Among the patients who participated in all three assessments, 80% of the subjects who met the criteria for acute stress disorder were diagnosed with PTSD at 2 years. Of the total initial group, 73% of those diagnosed with acute stress disorder had PTSD at 2 years. CONCLUSIONS: This study provides further support for the utility of the acute stress disorder diagnosis as a predictor of PTSD but indicates that the predictive power of the diagnostic criteria can be increased by placing greater emphasis on reexperiencing, avoidance, and arousal symptoms.


Assuntos
Lesões Encefálicas/complicações , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Acidentes de Trânsito/psicologia , Acidentes de Trânsito/estatística & dados numéricos , Doença Aguda , Adolescente , Adulto , Idoso , Nível de Alerta , Lesões Encefálicas/diagnóstico , Lesões Encefálicas/psicologia , Feminino , Seguimentos , Humanos , Masculino , Memória , Pessoa de Meia-Idade , Probabilidade , Estudos Prospectivos , Transtornos de Estresse Pós-Traumáticos/etiologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Estresse Psicológico/diagnóstico , Estresse Psicológico/etiologia , Estresse Psicológico/psicologia , Sobreviventes/psicologia , Sobreviventes/estatística & dados numéricos , Índices de Gravidade do Trauma
19.
Am J Psychiatry ; 155(5): 625-9, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-9585713

RESUMO

OBJECTIVE: The aim of this study was to index the frequency of occurrence of acute stress disorder following mild traumatic brain injury and to determine its utility in predicting posttraumatic stress disorder (PTSD). METHOD: Consecutive adult patients who sustained a mild traumatic brain injury following a motor vehicle accident (N = 79) were assessed for acute stress disorder within 1 month of their trauma with the Acute Stress Disorder Inventory, a structured clinical interview based on DSM-IV criteria. Patients were followed up 6 months after the trauma (N = 63) and were administered the PTSD module of the Composite International Diagnostic Interview. RESULTS: Acute stress disorder was diagnosed in 14% of patients, and at follow-up 24% satisfied criteria for PTSD. Six months after the trauma PTSD was diagnosed in 82% of patients who had been diagnosed with acute stress disorder and in 11% of those who had not been diagnosed with acute stress disorder. CONCLUSIONS: These findings point to the frequency of PTSD following mild traumatic brain injury. While the criteria for acute stress disorder are useful in identifying those individuals who are at risk of developing chronic PTSD, the findings suggest that current criteria require modification in order to optimally predict PTSD following mild traumatic brain injury.


Assuntos
Lesões Encefálicas/epidemiologia , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Estresse Psicológico/diagnóstico , Acidentes de Trânsito/psicologia , Doença Aguda , Adolescente , Adulto , Lesões Encefálicas/diagnóstico , Análise por Conglomerados , Comorbidade , Feminino , Seguimentos , Humanos , Acontecimentos que Mudam a Vida , Masculino , Pessoa de Meia-Idade , Probabilidade , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Fatores de Risco , Índice de Gravidade de Doença , Estresse Psicológico/epidemiologia
20.
Am J Psychiatry ; 157(4): 629-31, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10739426

RESUMO

OBJECTIVE: This study indexed the profile of posttraumatic stress disorder (PTSD) after severe traumatic injury to the brain. METHOD: Patients who sustained a severe traumatic brain injury (N=96) were assessed for PTSD 6 months after the injury with the PTSD Interview, a structured clinical interview based on DSM-III-R criteria. RESULTS: PTSD was diagnosed in 26 (27.1%) of the patients. While only 19.2% (N=5) of the patients with PTSD reported intrusive memories of the trauma, 96.2% (N=25) reported emotional reactivity. Intrusive memories, nightmares, and emotional reactivity had very strong positive predictive values for the presence of PTSD. CONCLUSIONS: These findings indicate that PTSD can develop after severe traumatic brain injury. The predominance of emotional reactivity and the relative absence of traumatic memories in patients with PTSD who suffered impaired consciousness during trauma suggest that traumatic experiences can mediate PTSD at an implicit level.


Assuntos
Lesões Encefálicas/complicações , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Adolescente , Adulto , Idoso , Amnésia/diagnóstico , Amnésia/psicologia , Nível de Alerta , Lesões Encefálicas/diagnóstico , Sonhos/psicologia , Humanos , Pessoa de Meia-Idade , Probabilidade , Estudos Prospectivos , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Transtornos de Estresse Pós-Traumáticos/etiologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Estresse Psicológico/diagnóstico , Estresse Psicológico/etiologia , Estresse Psicológico/psicologia , Índices de Gravidade do Trauma
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