RESUMO
BACKGROUND: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group. METHODS: We analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls using traditional machine learning methods. Second, we assessed the utility of the denoising variational autoencoder (DVAE) and evaluated its classification performance. Third, we assessed the generalizability and reproducibility of both models using leave-one-site-out cross-validation procedure for each modality. RESULTS: We found lower performance in classifying PTSD vs. controls with data from over 20 sites (60 % test AUC for s-MRI, 59 % for rs-fMRI and 56 % for d-MRI), as compared to other studies run on single-site data. The performance increased when classifying PTSD from HC without trauma history in each modality (75 % AUC). The classification performance remained intact when applying the DVAE framework, which reduced the number of features. Finally, we found that the DVAE framework achieved better generalization to unseen datasets compared with the traditional machine learning frameworks, albeit performance was slightly above chance. CONCLUSION: These results have the potential to provide a baseline classification performance for PTSD when using large scale neuroimaging datasets. Our findings show that the control group used can heavily affect classification performance. The DVAE framework provided better generalizability for the multi-site data. This may be more significant in clinical practice since the neuroimaging-based diagnostic DVAE classification models are much less site-specific, rendering them more generalizable.
Assuntos
Transtornos de Estresse Pós-Traumáticos , Humanos , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Reprodutibilidade dos Testes , Big Data , Neuroimagem , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagemRESUMO
Traumatic brain injury (TBI) in military populations can cause disruptions in brain structure and function, along with cognitive and psychological dysfunction. Diffusion magnetic resonance imaging (dMRI) can detect alterations in white matter (WM) microstructure, but few studies have examined brain asymmetry. Examining asymmetry in large samples may increase sensitivity to detect heterogeneous areas of WM alteration in mild TBI. Through the Enhancing Neuroimaging Genetics Through Meta-Analysis Military-Relevant Brain Injury working group, we conducted a mega-analysis of neuroimaging and clinical data from 16 cohorts of Active Duty Service Members and Veterans (n = 2598). dMRI data were processed together along with harmonized demographic, injury, psychiatric, and cognitive measures. Fractional anisotropy in the cingulum showed greater asymmetry in individuals with deployment-related TBI, driven by greater left lateralization in TBI. Results remained significant after accounting for potentially confounding variables including posttraumatic stress disorder, depression, and handedness, and were driven primarily by individuals whose worst TBI occurred before age 40. Alterations in the cingulum were also associated with slower processing speed and poorer set shifting. The results indicate an enhancement of the natural left laterality of the cingulum, possibly due to vulnerability of the nondominant hemisphere or compensatory mechanisms in the dominant hemisphere. The cingulum is one of the last WM tracts to mature, reaching peak FA around 42 years old. This effect was primarily detected in individuals whose worst injury occurred before age 40, suggesting that the protracted development of the cingulum may lead to increased vulnerability to insults, such as TBI.
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Lesões Encefálicas Traumáticas , Lesões Encefálicas , Substância Branca , Humanos , Adulto , Substância Branca/patologia , Testes Neuropsicológicos , Lesões Encefálicas/patologia , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Lesões Encefálicas Traumáticas/patologia , EncéfaloRESUMO
Mild Traumatic brain injury (mTBI) is a signature wound in military personnel, and repetitive mTBI has been linked to age-related neurogenerative disorders that affect white matter (WM) in the brain. However, findings of injury to specific WM tracts have been variable and inconsistent. This may be due to the heterogeneity of mechanisms, etiology, and comorbid disorders related to mTBI. Non-negative matrix factorization (NMF) is a data-driven approach that detects covarying patterns (components) within high-dimensional data. We applied NMF to diffusion imaging data from military Veterans with and without a self-reported TBI history. NMF identified 12 independent components derived from fractional anisotropy (FA) in a large dataset (n = 1,475) gathered through the ENIGMA (Enhancing Neuroimaging Genetics through Meta-Analysis) Military Brain Injury working group. Regressions were used to examine TBI- and mTBI-related associations in NMF-derived components while adjusting for age, sex, post-traumatic stress disorder, depression, and data acquisition site/scanner. We found significantly stronger age-dependent effects of lower FA in Veterans with TBI than Veterans without in four components (q < 0.05), which are spatially unconstrained by traditionally defined WM tracts. One component, occupying the most peripheral location, exhibited significantly stronger age-dependent differences in Veterans with mTBI. We found NMF to be powerful and effective in detecting covarying patterns of FA associated with mTBI by applying standard parametric regression modeling. Our results highlight patterns of WM alteration that are differentially affected by TBI and mTBI in younger compared to older military Veterans.
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Concussão Encefálica , Lesões Encefálicas Traumáticas , Lesões Encefálicas , Militares , Transtornos de Estresse Pós-Traumáticos , Veteranos , Substância Branca , Encéfalo/diagnóstico por imagem , Concussão Encefálica/diagnóstico por imagem , Lesões Encefálicas/etiologia , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Humanos , Análise Multivariada , Transtornos de Estresse Pós-Traumáticos/complicações , Substância Branca/diagnóstico por imagemRESUMO
A growing number of studies have examined alterations in white matter organization in people with posttraumatic stress disorder (PTSD) using diffusion MRI (dMRI), but the results have been mixed which may be partially due to relatively small sample sizes among studies. Altered structural connectivity may be both a neurobiological vulnerability for, and a result of, PTSD. In an effort to find reliable effects, we present a multi-cohort analysis of dMRI metrics across 3047 individuals from 28 cohorts currently participating in the PGC-ENIGMA PTSD working group (a joint partnership between the Psychiatric Genomics Consortium and the Enhancing NeuroImaging Genetics through Meta-Analysis consortium). Comparing regional white matter metrics across the full brain in 1426 individuals with PTSD and 1621 controls (2174 males/873 females) between ages 18-83, 92% of whom were trauma-exposed, we report associations between PTSD and disrupted white matter organization measured by lower fractional anisotropy (FA) in the tapetum region of the corpus callosum (Cohen's d = -0.11, p = 0.0055). The tapetum connects the left and right hippocampus, for which structure and function have been consistently implicated in PTSD. Results were consistent even after accounting for the effects of multiple potentially confounding variables: childhood trauma exposure, comorbid depression, history of traumatic brain injury, current alcohol abuse or dependence, and current use of psychotropic medications. Our results show that PTSD may be associated with alterations in the broader hippocampal network.
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Transtornos de Estresse Pós-Traumáticos , Substância Branca , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anisotropia , Encéfalo/diagnóstico por imagem , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adulto JovemRESUMO
Studies of posttraumatic stress disorder (PTSD) report volume abnormalities in multiple regions of the cerebral cortex. However, findings for many regions, particularly regions outside commonly studied emotion-related prefrontal, insular, and limbic regions, are inconsistent and tentative. Also, few studies address the possibility that PTSD abnormalities may be confounded by comorbid depression. A mega-analysis investigating all cortical regions in a large sample of PTSD and control subjects can potentially provide new insight into these issues. Given this perspective, our group aggregated regional volumes data of 68 cortical regions across both hemispheres from 1379 PTSD patients to 2192 controls without PTSD after data were processed by 32 international laboratories using ENIGMA standardized procedures. We examined whether regional cortical volumes were different in PTSD vs. controls, were associated with posttraumatic stress symptom (PTSS) severity, or were affected by comorbid depression. Volumes of left and right lateral orbitofrontal gyri (LOFG), left superior temporal gyrus, and right insular, lingual and superior parietal gyri were significantly smaller, on average, in PTSD patients than controls (standardized coefficients = -0.111 to -0.068, FDR corrected P values < 0.039) and were significantly negatively correlated with PTSS severity. After adjusting for depression symptoms, the PTSD findings in left and right LOFG remained significant. These findings indicate that cortical volumes in PTSD patients are smaller in prefrontal regulatory regions, as well as in broader emotion and sensory processing cortical regions.
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Transtornos de Estresse Pós-Traumáticos , Córtex Cerebral/diagnóstico por imagem , Genômica , Humanos , Imageamento por Ressonância Magnética , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Transtornos de Estresse Pós-Traumáticos/genética , Lobo TemporalRESUMO
BACKGROUND: Despite evidence linking posttraumatic stress disorder (PTSD), depression, and head injury, separately, with worse cognitive performance, investigations of their combined effects on cognition are limited in civilian women. METHODS: The Cogstate Brief Battery assessment was administered in 10,681 women from the Nurses' Health Study II cohort, mean age 64.9 years (SD = 4.6). Psychological trauma, PTSD, depression, and head injury were assessed using online questionnaires. In this cross-sectional analysis, we used linear regression models to estimate mean differences in cognition by PTSD/depression status and stratified by history of head injury. RESULTS: History of head injury was prevalent (36%), and significantly more prevalent among women with PTSD and depression (57% of women with PTSD and depression, 21% of women with no psychological trauma or depression). Compared to having no psychological trauma or depression, having combined PTSD and depression was associated with worse performance on psychomotor speed/attention ( ß = -.15, p = .001) and learning/working memory ( ß = -.15, p < .001). The joint association of PTSD and depression on worse cognitive function was strongest among women with past head injury, particularly among those with multiple head injuries. CONCLUSIONS: Head injury, like PTSD and depression, was highly prevalent in this sample of civilian women. In combination, these factors were associated with poorer performance on cognitive tasks, a possible marker of future cognitive health. Head injury should be further explored in future studies of PTSD, depression and cognition in women.
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Traumatismos Craniocerebrais , Transtornos de Estresse Pós-Traumáticos , Idoso , Cognição , Traumatismos Craniocerebrais/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Depressão/psicologia , Feminino , Humanos , Pessoa de Meia-Idade , Transtornos de Estresse Pós-Traumáticos/psicologiaRESUMO
BACKGROUND: A number of motor abnormalities have been reported in psychotic disorders, including dyskinesia and psychomotor slowing. There is also evidence for many of the same motor abnormalities in biological first-degree relatives and accruing evidence for motor abnormalities in bipolar disorder. In addition to motor dysfunction, there are also shared symptom domains amongst these populations. OBJECTIVES: We explored the associations of (1) current and lifetime psychosis and mood symptom domains and (2) domains of psychosis proneness with various domains of motor function in a transdiagnostic sample (n = 149). METHOD: Individuals with schizophrenia, schizoaffective disorder, or bipolar disorder, biological first-degree relatives of individuals with a psychotic disorder, and controls completed measures of psychomotor speed and movement fluidity, and neural activity related to motor preparation (stimulus-locked lateralized readiness potential, S-LRP) and execution (response-locked LRP) was assessed using EEG. All participants completed the Brief Psychiatric Rating Scale; patients were additionally assessed for lifetime psychosis and mood episode symptoms, and relatives and controls completed the Chapman psychosis proneness scales. RESULTS: Multiple regression revealed levels of current negative symptoms and mania were significantly positively associated with psychomotor slowing even after accounting for current antipsychotic medication dosage and duration of illness. S-LRP onset latency was significantly positively associated with magical ideation. CONCLUSION: Domains of motor function are associated with various mood and psychosis symptom domains in a transdiagnostic sample, which may provide insight into brain abnormalities relevant to the expression of symptoms across disorders.
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Transtorno Bipolar/fisiopatologia , Variação Contingente Negativa/fisiologia , Atividade Motora/fisiologia , Transtornos dos Movimentos/fisiopatologia , Desempenho Psicomotor/fisiologia , Transtornos Psicóticos/fisiopatologia , Esquizofrenia/fisiopatologia , Adulto , Transtorno Bipolar/epidemiologia , Comorbidade , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos dos Movimentos/epidemiologia , Transtornos Psicóticos/epidemiologia , Esquizofrenia/epidemiologiaRESUMO
Identifying the pathophysiology of posttraumatic stress disorder (PTSD) is a critical step toward reducing its debilitating impact. Spontaneous neural activity, measured at rest using various neuroimaging techniques (e.g., regional homogeneity [ReHo], amplitude of low frequency fluctuations [ALFF]), can provide insight about baseline neurobiological factors influencing sensory, cognitive, or behavioral processes associated with PTSD. The present study used activation likelihood estimation (ALE) to conduct the largest-to-date quantitative meta-analysis of spontaneous neural activity in PTSD, including 457 PTSD cases, 292 trauma-exposed controls (TECs), and 293 non-traumatized controls (NTCs) across 22 published studies. Five regions-of-interest (ROIs) were identified where activity differed between PTSD cases and controls: one when compared to all controls (left globus pallidus), two when compared to TECs (left inferior parietal lobule [IPL] and right lingual gyrus), and two when compared to NTCs (left amygdala and right caudate head). To corroborate these results, a second analysis was conducted using resting-state functional magnetic resonance imaging on an independent sample of 205 previously-deployed US military veterans. In this analysis, converging evidence from ReHo and ALFF showed that spontaneous neural activity in the left IPL alone was positively correlated with PTSD symptom severity. This result is consistent with theoretical accounts that link left IPL activity with PTSD-relevant processes such as processing of emotional stimuli (e.g., fearful faces) and the extent that attention is captured by salient autobiographical memories. By modeling the neurobiological correlates of PTSD, we can increase our understanding of this debilitating disorder and guide the development of future clinical innovations.
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Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Mapeamento Encefálico , Humanos , Imageamento por Ressonância Magnética , DescansoRESUMO
Attentional bias and self-referential schemas have been observed in numerous cross-sectional studies of depressed adults and are theorised to maintain negative mood. However, few longitudinal studies have examined whether maladaptive cognition predicts the course of depressive symptoms. Fifty-seven adults with elevated depression symptoms were assessed for negative attentional bias using a dot-probe task with eye-tracking and self-referential schemas using a self-referent encoding task. Participants subsequently completed five weekly depression symptom assessments. Participants with more negative self-referential schemas had higher baseline depression symptoms (r = .55). However, participants who spent more time attending to negative words showed greater symptom worsening over time (r = .42). The findings for negative self-referential schemas replicate past research, while the findings for negative attention bias represent the first evidence showing that attentional biases predict naturalistic symptom course. This work suggests that negative attention biases maintain depression symptoms and represent an important treatment target for neurocognitive therapeutics.
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Viés de Atenção , Depressão/diagnóstico , Depressão/psicologia , Autoimagem , Adolescente , Estudos Transversais , Feminino , Humanos , Masculino , Prognóstico , Adulto JovemRESUMO
In the 40 years since Aaron Beck first proposed his cognitive model of depression, the elements of this model--biased attention, biased processing, biased thoughts and rumination, biased memory, and dysfunctional attitudes and schemas--have been consistently linked with the onset and maintenance of depression. Although numerous studies have examined the neural mechanisms that underlie the cognitive aspects of depression, their findings have not been integrated with Beck's cognitive model. In this Review, we identify the functional and structural neurobiological architecture of Beck's cognitive model of depression. Although the mechanisms underlying each element of the model differ, in general the negative cognitive biases in depression are facilitated by increased influence from subcortical emotion processing regions combined with attenuated top-down cognitive control.
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Encéfalo/fisiopatologia , Cognição/fisiologia , Depressão/fisiopatologia , Transtorno Depressivo/fisiopatologia , Depressão/psicologia , Transtorno Depressivo/psicologia , Humanos , Modelos Neurológicos , Modelos PsicológicosRESUMO
Genetic variation within the serotonin system has been associated with biased attention for affective stimuli and, less consistently, with vulnerability for major depressive disorder. In particular, 5-HTTLPR, HTR1A (rs6295), and HTR2A (rs6311) polymorphisms have been linked with biased cognition. The present study developed a serotonergic cumulative genetic score (CGS) that quantified the number of risk alleles associated with these candidate polymorphisms to yield a single CGS. The CGS was then used to model genetic influence on the relationship between reactivity to a negative mood induction and negatively biased cognition. A passive-viewing eye-tracking task was administered to 170 healthy volunteers to assess sustained attention for positive, dysphoric, neutral, and threatening scenes. Participants were then induced into a sad mood and readministered the passive-viewing task. Change in gaze bias, as a function of reactivity to mood induction, was the primary measure of cognitive vulnerability. Results suggest that, although none of the individual genes interacted with mood reactivity to predict change in gaze bias, individuals with higher serotonin CGS were significantly more likely to look toward dysphoric images and away from positive images as mood reactivity increased. These findings suggest that a CGS approach may better capture genetic influences on cognitive vulnerability and reaffirm the need to examine multilocus approaches in genomic research.
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Afeto/fisiologia , Atenção/fisiologia , Viés , Fixação Ocular/genética , Polimorfismo de Nucleotídeo Único/genética , Receptor 5-HT1A de Serotonina/genética , Receptor 5-HT2A de Serotonina/genética , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Adulto , Feminino , Genótipo , Humanos , Masculino , Estimulação Luminosa , Análise de Regressão , Adulto JovemRESUMO
Blast-related mild traumatic brain injury (BR mTBI) is a critical research area in recent combat veterans due to increased prevalence of survived blasts. Post-BR mTBI outcomes are highly heterogeneous and defining neurological differences may help in discrimination and prediction of cognitive outcomes. This study investigates whether white matter integrity, measured with diffusion tensor imaging (DTI), could influence how remote BR mTBI history is associated with executive control. The sample included 151 Veterans from the Minneapolis Veterans Affairs Medical Center who were administered a clinical/TBI assessment, neuropsychological battery, and DTI scan as part of a larger battery. From previous research, six white matter tracts were identified as having a putative relationship with blast severity: the cingulum, hippocampal cingulum, corticospinal tract, inferior fronto-occipital fasciculus, superior longitudinal fasciculus and uncinate. Fractional anisotropy (FA) of the a priori selected white matter tracts and report of BR mTBI were used as predictors of Trail-Making Test B (TMT-B) performance in a multiple linear regression model. Statistical analysis revealed that FA of the hippocampal cingulum moderated the association between report of at least one BR mTBI and poorer TMT-B performance (p < 0.008), such that lower FA value was associated with worse TMT-B outcomes in individuals with BR mTBI. No significant moderation existed for other selected tracts, and the effect was not observed with predictors aside from history of BR mTBI. Investigation at the individual-tract level may lead to a deeper understanding of neurological differences between blast-related and non-blast related injuries.
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Traumatismos por Explosões , Concussão Encefálica , Imagem de Tensor de Difusão , Função Executiva , Veteranos , Substância Branca , Humanos , Masculino , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Traumatismos por Explosões/psicologia , Traumatismos por Explosões/diagnóstico por imagem , Traumatismos por Explosões/complicações , Imagem de Tensor de Difusão/métodos , Função Executiva/fisiologia , Adulto , Concussão Encefálica/diagnóstico por imagem , Concussão Encefálica/fisiopatologia , Concussão Encefálica/psicologia , Concussão Encefálica/patologia , Feminino , Testes Neuropsicológicos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Pessoa de Meia-Idade , AnisotropiaRESUMO
BACKGROUND: The 2023 VA/DoD Clinical Practice Guideline for the Management of PTSD recommends individual, manualized trauma-focused such as Prolonged Exposure (PE) over pharmacologic interventions for the primary treatment of PTSD. Unfortunately, clinical trials of trauma-based therapies in the military and veteran population showed that 30% to 50% of patients did not demonstrate clinically meaningful symptom change. Ketamine, an FDA-approved anesthetic with potent non-competitive glutamatergic N-methyl-d-aspartate antagonistic properties, has demonstrated to enhance the recall of extinction learning and decrease fear renewal without interference of extinction training in preclinical studies. METHODS: We plan to conduct a single site RCT comparing three ketamine treatment vs. active placebo (midazolam) adjunct to PE therapy among Veterans with PTSD. Pharmacological phase will start simultaneously with PE session 1. Infusions will be administered 24 h. prior to PE session for the first 3 weeks. After PE is completed (session 10), patients will be assessed during a 3-month follow-up period at various time points. We estimate that out of 100 veterans, 80 will reach time point for primary outcome measure and will be considered for primary analysis. Secondary outcomes include severity of depression and anxiety scores, safety and tolerability of ketamine-enhanced PE therapy, cognitive performance during treatment and early improvement during PE related to the rate of dropouts during PE therapy. DISCUSSION: Results of the proposed RCT could provide scientific foundation to distinguish the essential components of this approach, enhance the methodology, elucidate the mechanisms involved, and identify sub-PTSD populations that most likely benefit from this intervention.
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Terapia Implosiva , Ketamina , Transtornos de Estresse Pós-Traumáticos , Veteranos , Ketamina/administração & dosagem , Ketamina/uso terapêutico , Humanos , Transtornos de Estresse Pós-Traumáticos/terapia , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Veteranos/psicologia , Terapia Implosiva/métodos , Midazolam/uso terapêutico , Midazolam/administração & dosagem , Terapia Combinada , Masculino , Adulto , Método Duplo-CegoRESUMO
Resting state functional magnetic resonance imaging (rsfMRI) provides researchers and clinicians with a powerful tool to examine functional connectivity across large-scale brain networks, with ever-increasing applications to the study of neurological disorders, such as traumatic brain injury (TBI). While rsfMRI holds unparalleled promise in systems neurosciences, its acquisition and analytical methodology across research groups is variable, resulting in a literature that is challenging to integrate and interpret. The focus of this narrative review is to address the primary methodological issues including investigator decision points in the application of rsfMRI to study the consequences of TBI. As part of the ENIGMA Brain Injury working group, we have collaborated to identify a minimum set of recommendations that are designed to produce results that are reliable, harmonizable, and reproducible for the TBI imaging research community. Part one of this review provides the results of a literature search of current rsfMRI studies of TBI, highlighting key design considerations and data processing pipelines. Part two outlines seven data acquisition, processing, and analysis recommendations with the goal of maximizing study reliability and between-site comparability, while preserving investigator autonomy. Part three summarizes new directions and opportunities for future rsfMRI studies in TBI patients. The goal is to galvanize the TBI community to gain consensus for a set of rigorous and reproducible methods, and to increase analytical transparency and data sharing to address the reproducibility crisis in the field.
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Lesões Encefálicas Traumáticas , Imageamento por Ressonância Magnética , Humanos , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Lesões Encefálicas Traumáticas/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/normas , Reprodutibilidade dos Testes , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Descanso/fisiologia , Processamento de Imagem Assistida por Computador/métodos , Processamento de Imagem Assistida por Computador/normas , Mapeamento Encefálico/métodos , Mapeamento Encefálico/normasRESUMO
Posttraumatic stress disorder (PTSD) is associated with lower cortical thickness (CT) in prefrontal, cingulate, and insular cortices in diverse trauma-affected samples. However, some studies have failed to detect differences between PTSD patients and healthy controls or reported that PTSD is associated with greater CT. Using data-driven dimensionality reduction, we sought to conduct a well-powered study to identify vulnerable networks without regard to neuroanatomic boundaries. Moreover, this approach enabled us to avoid the excessive burden of multiple comparison correction that plagues vertex-wise methods. We derived structural covariance networks (SCNs) by applying non-negative matrix factorization (NMF) to CT data from 961 PTSD patients and 1124 trauma-exposed controls without PTSD. We used regression analyses to investigate associations between CT within SCNs and PTSD diagnosis (with and without accounting for the potential confounding effect of trauma type) and symptom severity in the full sample. We performed additional regression analyses in subsets of the data to examine associations between SCNs and comorbid depression, childhood trauma severity, and alcohol abuse. NMF identified 20 unbiased SCNs, which aligned closely with functionally defined brain networks. PTSD diagnosis was most strongly associated with diminished CT in SCNs that encompassed the bilateral superior frontal cortex, motor cortex, insular cortex, orbitofrontal cortex, medial occipital cortex, anterior cingulate cortex, and posterior cingulate cortex. CT in these networks was significantly negatively correlated with PTSD symptom severity. Collectively, these findings suggest that PTSD diagnosis is associated with widespread reductions in CT, particularly within prefrontal regulatory regions and broader emotion and sensory processing cortical regions.
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Transtornos de Estresse Pós-Traumáticos , Humanos , Transtornos de Estresse Pós-Traumáticos/psicologia , Imageamento por Ressonância Magnética , Encéfalo , Emoções , Córtex Pré-FrontalRESUMO
Background: Intrusive traumatic re-experiencing domain (ITRED) was recently introduced as a novel perspective on posttraumatic psychopathology, proposing to focus research of posttraumatic stress disorder (PTSD) on the unique symptoms of intrusive and involuntary re-experiencing of the trauma, namely, intrusive memories, nightmares, and flashbacks. The aim of the present study was to explore ITRED from a neural network connectivity perspective. Methods: Data were collected from 9 sites taking part in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) PTSD Consortium (n= 584) and included itemized PTSD symptom scores and resting-state functional connectivity (rsFC) data. We assessed the utility of rsFC in classifying PTSD, ITRED-only (no PTSD diagnosis), and trauma-exposed (TE)-only (no PTSD or ITRED) groups using a machine learning approach, examining well-known networks implicated in PTSD. A random forest classification model was built on a training set using cross-validation, and the averaged cross-validation model performance for classification was evaluated using the area under the curve. The model was tested using a fully independent portion of the data (test dataset), and the test area under the curve was evaluated. Results: rsFC signatures differentiated TE-only participants from PTSD and ITRED-only participants at about 60% accuracy. Conversely, rsFC signatures did not differentiate PTSD from ITRED-only individuals (45% accuracy). Common features differentiating TE-only participants from PTSD and ITRED-only participants mainly involved default mode network-related pathways. Some unique features, such as connectivity within the frontoparietal network, differentiated TE-only participants from one group (PTSD or ITRED-only) but to a lesser extent from the other group. Conclusions: Neural network connectivity supports ITRED as a novel neurobiologically based approach to classifying posttrauma psychopathology.
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Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15-90. The effects of dementia, mild cognitive impairment, Parkinson's disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals. Random forest models identified age, years of education, and site as important VLM covariates. A Bayesian harmonization approach was used to isolate and remove site effects. Regression estimated the adjusted association of each clinical group with VLM scores. Memory deficits were strongly associated with dementia and schizophrenia (p < 0.001), while neither depression nor ADHD showed consistent associations with VLM scores (p > 0.05). Differences associated with clinical conditions were larger for longer delayed recall duration items. By comparing VLM across clinical conditions, this study provides a foundation for enhanced diagnostic precision and offers new insights into disease management of comorbid disorders.
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OBJECTIVE: Memory complaints are the most common form of cognitive limitation reported by military service members, but prior research suggests that posttraumatic stress symptoms (PTSS) may account for the link between subjective cognitive complaints and objective cognitive performance. The mechanisms underlying this relationship are largely unknown, including whether the finding applies to memory complaints and performance, which clinical dimensions are involved, and how the association varies when memory complaints are non-credible. METHOD: Using a sample of 196 US military service members, the present study aims to address these gaps by modeling the relationship between objective memory performance and plausible/implausible subjective memory complaints, then evaluating how the association is influenced by PTSS and clinical traits commonly found within PTSS (e.g. depression, anxiety, and somatic concerns). RESULTS: Overall memory complaints were associated with immediate and delayed recall, but both associations were fully mediated by PTSS (95% CI -0.14, -0.01; 95% CI -0.14, -0.02, respectively). Implausible memory complaints, however, were inconsistently linked to memory performance, and no PTSS mediation was observed. Of the clinical traits, only depression moderated the impact of PTSS, specifically by influencing the link between PTSS and overall memory complaints (ß = -0.02, SE = 0.004, p < .001). CONCLUSIONS: These results corroborate the importance of assessment for PTSS and depression in service members who report subjective memory complaints and highlight how targeted intervention for these conditions may play a key role in the management of memory complaints.
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Transtornos de Estresse Pós-Traumáticos , Humanos , Transtornos de Estresse Pós-Traumáticos/psicologia , Testes Neuropsicológicos , Ansiedade/psicologia , Transtornos de AnsiedadeRESUMO
There is a public health need to understand mental health vulnerabilities to COVID-19 pandemic-related stressors and promote resilience among high-risk populations with preexisting psychiatric conditions. Recent cross-sectional studies suggest increases in mental health distress (e.g., depression and anxiety) during the pandemic. The present study expands upon these emerging findings using longitudinal latent modeling and hierarchical linear regressions. Consistent with the developmental psychopathology literature on resilience, we distinguished between promotive or risk (i.e., main effect), and protective or vulnerability (i.e., moderation) effects on mental health during the pandemic. At a large medical center, 398 veterans receiving outpatient mental health care provided prepandemic (Time 1) and during pandemic (Time 2) assessments of mental and physical health-related distress. Additional Time 2 questionnaires assessed pandemic-related stressors and positive behavioral adaptations in the summer of 2020. As expected, total stressor scores predicted longitudinal worsening of self-reported mental (ß = -.205) and physical health (ß = -.217). Positive behavioral adaptations enacted during the pandemic moderated and protected against stressor effects on mental health (ß = .160). In addition, the presence of substance use disorders moderated and conferred vulnerability to stressor effects on physical health (ß = -.158). Thus, higher COVID-19 pandemic stressor exposure may have exacerbated mental and physical health distress among veterans with common forms of psychopathology. Nevertheless, behavioral activation, purposeful maintenance of social connections, and focused treatment for substance misuse may be important intervention targets for reducing the longitudinal impact of pandemic stressors and enhancing resilience among people with mental illness. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
Assuntos
COVID-19 , Veteranos , Humanos , Saúde Mental , Pandemias , Pacientes AmbulatoriaisRESUMO
Investigators in neuroscience have turned to Big Data to address replication and reliability issues by increasing sample sizes, statistical power, and representativeness of data. These efforts unveil new questions about integrating data arising from distinct sources and instruments. We focus on the most frequently assessed cognitive domain - memory testing - and demonstrate a process for reliable data harmonization across three common measures. We aggregated global raw data from 53 studies totaling N = 10,505 individuals. A mega-analysis was conducted using empirical bayes harmonization to remove site effects, followed by linear models adjusting for common covariates. A continuous item response theory (IRT) model estimated each individual's latent verbal learning ability while accounting for item difficulties. Harmonization significantly reduced inter-site variance while preserving covariate effects, and our conversion tool is freely available online. This demonstrates that large-scale data sharing and harmonization initiatives can address reproducibility and integration challenges across the behavioral sciences.