RESUMO
BACKGROUND: There is a growing population of children with in utero HIV exposure who are at risk of poor neurodevelopmental outcomes despite avoiding HIV infection. However, the underlying neurobiological pathways are not understood and neuroimaging studies are lacking. We aimed to investigate the cortical brain structure of children who are HIV-exposed and uninfected (HEU) compared to HIV-unexposed (HU) children and to examine the relationship with neurodevelopment. METHODS: The Drakenstein Child Health birth cohort study enrolled pregnant women from a high HIV prevalence area in South Africa with longitudinal follow-up of mother-child pairs. High-resolution magnetic resonance imaging scans from 162 children (70 HEU; 92 HU) were acquired at 2-3 years of age. All HEU children were born to mothers taking antiretroviral therapy. Measures of brain structure (cortical thickness and surface area) in the prefrontal cortex regions were extracted from T1-weighted images and compared between groups using multivariate analysis of variance and linear regression. Child development, assessed using the Bayley Scales of Infant and Toddler Development-III, was correlated with cortical structure, and mediation analyses were performed. RESULTS: Analyses demonstrated an association between HIV exposure and cortical thickness across the prefrontal cortex (p = 0.035). Children who were HEU had thicker cortices in prefrontal regions, with significantly greater cortical thickness in the medial orbitofrontal cortex (mOFC) bilaterally compared to HU children (3.21 mm versus 3.14 mm, p = 0.009, adjusted effect size 0.44 [95% CI 0.12 to 0.75]). Estimates held across multiple sensitivity analyses. There were no group differences in cortical surface area. Language scores, which were lower in HEU versus HU children (81.82 versus 86.25, p = 0.011, effect size - 0.44 [95% CI - 0.78 to - 0.09]), negatively correlated with prefrontal cortical thickness in both groups. Cortical thickness in the mOFC mediated the relationship between HIV exposure and poor language outcomes (Sobel test p = 0.032). CONCLUSIONS: In this cohort study, exposure to HIV during pregnancy was associated with altered cortical structure in early life. Our findings indicate that differences in cortical thickness development in the prefrontal region in children who are HEU may be a pathway leading to language impairment. Longitudinal studies are needed to determine the lasting impact.
Assuntos
Infecções por HIV , Complicações Infecciosas na Gravidez , Lactente , Humanos , Gravidez , Feminino , Complicações Infecciosas na Gravidez/diagnóstico por imagem , Complicações Infecciosas na Gravidez/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Estudos de Coortes , África do Sul/epidemiologia , Estudos Prospectivos , Encéfalo/diagnóstico por imagemRESUMO
The current small study utilised prospective data collection of patterns of prenatal alcohol and tobacco exposure (PAE and PTE) to examine associations with structural brain outcomes in 6-year-olds and served as a pilot to determine the value of prospective data describing community-level patterns of PAE and PTE in a non-clinical sample of children. Participants from the Safe Passage Study in pregnancy were approached when their child was â¼6 years old and completed structural brain magnetic resonance imaging to examine with archived PAE and PTE data (n = 51 children-mother dyads). Linear regression was used to conduct whole-brain structural analyses, with false-discovery rate (FDR) correction, to examine: (a) main effects of PAE, PTE and their interaction; and (b) predictive potential of data that reflect patterns of PAE and PTE (e.g. quantity, frequency and timing (QFT)). Associations between PAE, PTE and their interaction with brain structural measures demonstrated unique profiles of cortical and subcortical alterations that were distinct between PAE only, PTE only and their interactive effects. Analyses examining associations between patterns of PAE and PTE (e.g. QFT) were able to significantly detect brain alterations (that survived FDR correction) in this small non-clinical sample of children. These findings support the hypothesis that considering QFT and co-exposures is important for identifying brain alterations following PAE and/or PTE in a small group of young children. Current results demonstrate that teratogenic outcomes on brain structure differ as a function PAE, PTE or their co-exposures, as well as the pattern (QFT) or exposure.
Assuntos
Efeitos Tardios da Exposição Pré-Natal , Criança , Gravidez , Feminino , Humanos , Pré-Escolar , Projetos Piloto , África do Sul , Encéfalo/patologia , Imageamento por Ressonância MagnéticaRESUMO
Patients with obstructive sleep apnea (OSA) show autonomic, mood, cognitive, and breathing dysfunctions that are linked to increased morbidity and mortality, which can be improved with early screening and intervention. The gold standard and other available methods for OSA diagnosis are complex, require whole-night data, and have significant wait periods that potentially delay intervention. Our aim was to examine whether using faster and less complicated machine learning models, including support vector machine (SVM) and random forest (RF), with brain diffusion tensor imaging (DTI) data can classify OSA from healthy controls. We collected two DTI series from 59 patients with OSA [age: 50.2 ± 9.9 years; body mass index (BMI): 31.5 ± 5.6 kg/m2 ; apnea-hypopnea index (AHI): 34.1 ± 21.2 events/h 23 female] and 96 controls (age: 51.8 ± 9.7 years; BMI: 26.2 ± 4.1 kg/m2 ; 51 female) using a 3.0-T magnetic resonance imaging scanner. Using DTI data, mean diffusivity maps were calculated from each series, realigned and averaged, normalised to a common space, and used to conduct cross-validation for model training and selection and to predict OSA. The RF model showed 0.73 OSA and controls classification accuracy and 0.85 area under the curve (AUC) value on the receiver-operator curve. Cross-validation showed the RF model with comparable fitting over SVM for OSA and control data (SVM; accuracy, 0.77; AUC, 0.84). The RF ML model performs similar to SVM, indicating the comparable statistical fitness to DTI data. The findings indicate that RF model has similar AUC and accuracy over SVM, and either model can be used as a faster OSA screening tool for subjects having brain DTI data.
Assuntos
Imagem de Tensor de Difusão , Apneia Obstrutiva do Sono , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Apneia Obstrutiva do Sono/diagnóstico por imagem , Apneia Obstrutiva do Sono/patologia , Encéfalo , Índice de Massa Corporal , Aprendizado de MáquinaRESUMO
BACKGROUND: Ketamine is a rapidly-acting antidepressant treatment with robust response rates. Previous studies have reported that serial ketamine therapy modulates resting state functional connectivity in several large-scale networks, though it remains unknown whether variations in brain structure, function, and connectivity impact subsequent treatment success. We used a data-driven approach to determine whether pretreatment multimodal neuroimaging measures predict changes along symptom dimensions of depression following serial ketamine infusion. METHODS: Patients with depression (n = 60) received structural, resting state functional, and diffusion MRI scans before treatment. Depressive symptoms were assessed using the 17-item Hamilton Depression Rating Scale (HDRS-17), the Inventory of Depressive Symptomatology (IDS-C), and the Rumination Response Scale (RRS) before and 24 h after patients received four (0.5 mg/kg) infusions of racemic ketamine over 2 weeks. Nineteen unaffected controls were assessed at similar timepoints. Random forest regression models predicted symptom changes using pretreatment multimodal neuroimaging and demographic measures. RESULTS: Two HDRS-17 subscales, the HDRS-6 and core mood and anhedonia (CMA) symptoms, and the RRS: reflection (RRSR) scale were predicted significantly with 19, 27, and 1% variance explained, respectively. Increased right medial prefrontal cortex/anterior cingulate and posterior insula (PoI) and lower kurtosis of the superior longitudinal fasciculus predicted reduced HDRS-6 and CMA symptoms following treatment. RRSR change was predicted by global connectivity of the left posterior cingulate, left insula, and right superior parietal lobule. CONCLUSIONS: Our findings support that connectivity of the anterior default mode network and PoI may serve as potential biomarkers of antidepressant outcomes for core depressive symptoms.
Assuntos
Transtorno Depressivo Maior , Ketamina , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Rede de Modo Padrão , Depressão/diagnóstico por imagem , Depressão/tratamento farmacológico , Humanos , Ketamina/farmacologia , Imageamento por Ressonância Magnética/métodosRESUMO
BACKGROUND: Subanesthetic ketamine infusion therapy can produce fast-acting antidepressant effects in patients with major depression. How single and repeated ketamine treatment modulates the whole-brain functional connectome to affect clinical outcomes remains uncharacterized. METHODS: Data-driven whole brain functional connectivity (FC) analysis was used to identify the functional connections modified by ketamine treatment in patients with major depressive disorder (MDD). MDD patients (N = 61, mean age = 38, 19 women) completed baseline resting-state (RS) functional magnetic resonance imaging and depression symptom scales. Of these patients, n = 48 and n = 51, completed the same assessments 24 h after receiving one and four 0.5 mg/kg intravenous ketamine infusions. Healthy controls (HC) (n = 40, 24 women) completed baseline assessments with no intervention. Analysis of RS FC addressed effects of diagnosis, time, and remitter status. RESULTS: Significant differences (p < 0.05, corrected) in RS FC were observed between HC and MDD at baseline in the somatomotor network and between association and default mode networks. These disruptions in FC in MDD patients trended toward control patterns with ketamine treatment. Furthermore, following serial ketamine infusions, significant decreases in FC were observed between the cerebellum and salience network (SN) (p < 0.05, corrected). Patient remitters showed increased FC between the cerebellum and the striatum prior to treatment that decreased following treatment, whereas non-remitters showed the opposite pattern. CONCLUSION: Results support that ketamine treatment leads to neurofunctional plasticity between distinct neural networks that are shown as disrupted in MDD patients. Cortico-striatal-cerebellar loops that encompass the SN could be a potential biomarker for ketamine treatment.
Assuntos
Conectoma , Transtorno Depressivo Maior , Ketamina , Humanos , Feminino , Conectoma/métodos , Imageamento por Ressonância Magnética/métodos , EncéfaloRESUMO
Electroconvulsive therapy (ECT) has been repeatedly linked to hippocampal plasticity. However, it remains unclear what role hippocampal plasticity plays in the antidepressant response to ECT. This magnetic resonance imaging (MRI) study tracks changes in separate hippocampal subregions and hippocampal networks in patients with depression (n = 44, 23 female) to determine their relationship, if any, with improvement after ECT. Voxelwise analyses were restricted to the hippocampus, amygdala, and parahippocampal cortex, and applied separately for responders and nonresponders to ECT. In analyses of arterial spin-labeled (ASL) MRI, nonresponders exhibited increased cerebral blood flow (CBF) in bilateral anterior hippocampus, while responders showed CBF increases in right middle and left posterior hippocampus. In analyses of gray matter volume (GMV) using T1-weighted MRI, GMV increased throughout bilateral hippocampus and surrounding tissue in nonresponders, while responders showed increased GMV in right anterior hippocampus only. Using CBF loci as seed regions, BOLD-fMRI data from healthy controls (n = 36, 19 female) identified spatially separable neurofunctional networks comprised of different brain regions. In graph theory analyses of these networks, functional connectivity within a hippocampus-thalamus-striatum network decreased only in responders after two treatments and after index. In sum, our results suggest that the location of ECT-related plasticity within the hippocampus may differ according to antidepressant outcome, and that larger amounts of hippocampal plasticity may not be conducive to positive antidepressant response. More focused targeting of hippocampal subregions and/or circuits may be a way to improve ECT outcome.
Assuntos
Transtorno Depressivo Maior , Eletroconvulsoterapia , Antidepressivos , Encéfalo , Transtorno Depressivo Maior/tratamento farmacológico , Feminino , Hipocampo , Humanos , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: There is a growing literature that demonstrates the effects of prenatal alcohol exposure (PAE) on brain development in school-aged children. Less is known, however, on how PAE impacts the brain early in life. We investigated the effects of PAE and child sex on subcortical gray matter volume, cortical surface area (CSA), cortical volume (CV), and cortical thickness (CT) in children aged 2 to 3 years. METHODS: The sample was recruited as a nested cross-sectional substudy of the Drakenstein Child Health Study. Images from T1-weighted magnetic resonance imaging were acquired on 47 alcohol-exposed and 124 control children (i.e., with no or minimal alcohol exposure), aged 2 to 3 years, some of whom were scanned as neonates. Brain images were processed through automated processing pipelines using FreeSurfer version 6.0. Subcortical and a priori selected cortical regions of interest were compared. RESULTS: Subcortical volume analyses revealed a PAE by child sex interaction for bilateral putamen volumes (Left: p = 0.02; Right: p = 0.01). There was no PAE by child sex interaction effect on CSA, CV, and CT. Analyses revealed an impact of PAE on CSA (p = 0.04) and CV (p = 0.04), but not CT in this age group. Of note, the inferior parietal gyrus CSA was significantly smaller in children with PAE compared to control children. CONCLUSIONS: Findings from this subgroup scanned at age 2 to 3 years build on previously described subcortical volume differences in neonates from this cohort. Findings suggest that PAE persistently affects gray matter development through the critical early years of life. The detectable influence of PAE on brain structure at this early age further highlights the importance of brain imaging studies on the impact of PAE on the young developing brain.
Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Substância Cinzenta , Efeitos Tardios da Exposição Pré-Natal , Coorte de Nascimento , Encéfalo , Criança , Pré-Escolar , Estudos Transversais , Feminino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética/métodos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/diagnóstico por imagem , Efeitos Tardios da Exposição Pré-Natal/patologia , África do Sul/epidemiologiaRESUMO
BACKGROUND: Neuroimaging studies have emphasized the impact of prenatal alcohol exposure (PAE) on brain development, traditionally in heavily exposed participants. However, less is known about how naturally occurring community patterns of PAE (including light to moderate exposure) affect brain development, particularly in consideration of commonly occurring concurrent impacts of prenatal tobacco exposure (PTE). METHODS: Three hundred thirty-two children (ages 8 to 12) living in South Africa's Cape Flats townships underwent structural magnetic resonance imaging. During pregnancy, their mothers reported alcohol and tobacco use, which was used to evaluate PAE and PTE effects on their children's brain structure. Analyses involved the main effects of PAE and PTE (and their interaction) and the effects of PAE and PTE quantity on cortical thickness, surface area, and volume. RESULTS: After false-discovery rate (FDR) correction, PAE was associated with thinner left parahippocampal cortices, while PTE was associated with smaller cortical surface area in the bilateral pericalcarine, left lateral orbitofrontal, right posterior cingulate, right rostral anterior cingulate, left caudal middle frontal, and right caudal anterior cingulate gyri. There were no PAE × PTE interactions nor any associations of PAE and PTE exposure on volumetrics that survived FDR correction. CONCLUSION: PAE was associated with reduction in the structure of the medial temporal lobe, a brain region critical for learning and memory. PTE had stronger and broader associations, including with regions associated with executive function, reward processing, and emotional regulation, potentially reflecting continued postnatal exposure to tobacco (i.e., second-hand smoke exposure). These differential effects are discussed with respect to reduced PAE quantity in our exposed group versus prior studies within this geographical location, the deep poverty in which participants live, and the consequences of apartheid and racially and economically driven payment practices that contributed to heavy drinking in the region. Longer-term follow-up is needed to determine potential environmental and other moderators of the brain findings here and assess the extent to which they endure over time.
Assuntos
Nicotiana , Efeitos Tardios da Exposição Pré-Natal , Criança , Humanos , Feminino , Gravidez , Nicotiana/efeitos adversos , África do Sul/epidemiologia , Coorte de Nascimento , Efeitos Tardios da Exposição Pré-Natal/diagnóstico por imagem , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/patologia , Encéfalo , Etanol/farmacologiaRESUMO
Depression symptom heterogeneity limits the identifiability of treatment-response biomarkers. Whether improvement along dimensions of depressive symptoms relates to separable neural networks remains poorly understood. We build on work describing three latent symptom dimensions within the 17-item Hamilton Depression Rating Scale (HDRS) and use data-driven methods to relate multivariate patterns of patient clinical, demographic, and brain structural changes over electroconvulsive therapy (ECT) to dimensional changes in depressive symptoms. We included 110 ECT patients from Global ECT-MRI Research Collaboration (GEMRIC) sites who underwent structural MRI and HDRS assessments before and after treatment. Cross validated random forest regression models predicted change along symptom dimensions. HDRS symptoms clustered into dimensions of somatic disturbances (SoD), core mood and anhedonia (CMA), and insomnia. The coefficient of determination between predicted and actual changes were 22%, 39%, and 39% (all p < .01) for SoD, CMA, and insomnia, respectively. CMA and insomnia change were predicted more accurately than HDRS-6 and HDRS-17 changes (p < .05). Pretreatment symptoms, body-mass index, and age were important predictors. Important imaging predictors included the right transverse temporal gyrus and left frontal pole for the SoD dimension; right transverse temporal gyrus and right rostral middle frontal gyrus for the CMA dimension; and right superior parietal lobule and left accumbens for the insomnia dimension. Our findings support that recovery along depressive symptom dimensions is predicted more accurately than HDRS total scores and are related to unique and overlapping patterns of clinical and demographic data and volumetric changes in brain regions related to depression and near ECT electrodes.
Assuntos
Córtex Cerebral/patologia , Transtorno Depressivo Maior/patologia , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/terapia , Eletroconvulsoterapia , Aprendizado de Máquina , Neuroimagem/normas , Avaliação de Resultados em Cuidados de Saúde/normas , Adulto , Idoso , Córtex Cerebral/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem/métodos , Avaliação de Resultados em Cuidados de Saúde/métodosRESUMO
Multiple system atrophy (MSA) is a rare neurodegenerative disorder characterized by the widespread aberrant accumulation of α-synuclein (α-syn). MSA differs from other synucleinopathies such as Parkinson's disease (PD) in that α-syn accumulates primarily in oligodendrocytes, the only source of white matter myelination in the brain. Previous MSA imaging studies have uncovered focal differences in white matter. Here, we sought to build on this work by taking a global perspective on whole brain white matter. In order to do this, in vivo structural imaging and diffusion magnetic resonance imaging were acquired on 26 MSA patients, 26 healthy controls, and 23 PD patients. A refined whole brain approach encompassing the major fiber tracts and the superficial white matter located at the boundary of the cortical mantle was applied. The primary observation was that MSA but not PD patients had whole brain deep and superficial white matter diffusivity abnormalities (p < .001). In addition, in MSA patients, these abnormalities were associated with motor (Unified MSA Rating Scale, Part II) and cognitive functions (Mini-Mental State Examination). The pervasive whole brain abnormalities we observe suggest that there is widespread white matter damage in MSA patients which mirrors the widespread aggregation of α-syn in oligodendrocytes. Importantly, whole brain white matter abnormalities were associated with clinical symptoms, suggesting that white matter impairment may be more central to MSA than previously thought.
Assuntos
Imageamento por Ressonância Magnética/métodos , Atrofia de Múltiplos Sistemas/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas/fisiopatologia , Substância Branca/fisiopatologiaRESUMO
Magnetic resonance imaging (MRI) is an indispensable tool for investigating brain development in young children and the neurobiological mechanisms underlying developmental risk and resilience. Sub-Saharan Africa has the highest proportion of children at risk of developmental delay worldwide, yet in this region there is very limited neuroimaging research focusing on the neurobiology of such impairment. Furthermore, paediatric MRI imaging is challenging in any setting due to motion sensitivity. Although sedation and anesthesia are routinely used in clinical practice to minimise movement in young children, this may not be ethical in the context of research. Our study aimed to investigate the feasibility of paediatric multimodal MRI at age 2-3 years without sedation, and to explore the relationship between cortical structure and neurocognitive development at this understudied age in a sub-Saharan African setting. A total of 239 children from the Drakenstein Child Health Study, a large observational South African birth cohort, were recruited for neuroimaging at 2-3 years of age. Scans were conducted during natural sleep utilising locally developed techniques. T1-MEMPRAGE and T2-weighted structural imaging, resting state functional MRI, diffusion tensor imaging and magnetic resonance spectroscopy sequences were included. Child neurodevelopment was assessed using the Bayley-III Scales of Infant and Toddler Development. Following 23 pilot scans, 216 children underwent scanning and T1-weighted images were obtained from 167/216 (77%) of children (median age 34.8 months). Furthermore, we found cortical surface area and thickness within frontal regions were associated with cognitive development, and in temporal and frontal regions with language development (beta coefficient ≥0.20). Overall, we demonstrate the feasibility of carrying out a neuroimaging study of young children during natural sleep in sub-Saharan Africa. Our findings indicate that dynamic morphological changes in heteromodal association regions are associated with cognitive and language development at this young age. These proof-of-concept analyses suggest similar links between the brain and cognition as prior literature from high income countries, enhancing understanding of the interplay between cortical structure and function during brain maturation.
Assuntos
Encéfalo/diagnóstico por imagem , Desenvolvimento Infantil/fisiologia , Cognição/fisiologia , Encéfalo/fisiologia , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Neuroimagem , África do SulRESUMO
Electroconvulsive therapy (ECT) and ketamine treatment both induce rapidly acting antidepressant effects in patients with major depressive disorder unresponsive to standard treatments, yet their specific impact on emotion processing is unknown. Here, we examined the neural underpinnings of emotion processing within and across patients (N = 44) receiving either ECT (N = 17, mean age: 36.8, 11.0 SD) or repeated subanesthetic (0.5 mg/kg) intravenous ketamine therapy (N = 27, mean age: 37.3, 10.8 SD) using a naturalistic study design. MRI and clinical data were collected before (TP1) and after treatment (TP2); healthy controls (N = 31, mean age: 34.5, 13.5 SD) completed one MRI session (TP1). An fMRI face-matching task probed negative- and positive-valence systems. Whole-brain analysis, comparing neurofunctional changes within and across treatment groups, targeted brain regions involved in emotional facial processing, and included regions-of-interest analysis of amygdala responsivity. Main findings revealed a decrease in amygdalar reactivity after both ECT and ketamine for positive and negative emotional face processing (p < .05 family wise-error (FWE) corrected). Subthreshold changes were observed between treatments within the dorsolateral prefrontal cortex and insula (p < .005, uncorrected). BOLD change for positive faces in the inferior parietal cortex significantly correlated with overall symptom improvement, and BOLD change in frontal regions correlated with anxiety for negative faces, and anhedonia for positive faces (p < .05 FWE corrected). Both serial ketamine and ECT treatment modulate amygdala response, while more subtle treatment-specific changes occur in the larger functional network. Findings point to both common and differential mechanistic upstream systems-level effects relating to fast-acting antidepressant response, and symptoms of anxiety and anhedonia, for the processing of emotionally valenced stimuli.
Assuntos
Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/fisiopatologia , Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/psicologia , Transtorno Depressivo Maior/terapia , Eletroconvulsoterapia , Ketamina/uso terapêutico , Adulto , Antidepressivos/administração & dosagem , Mapeamento Encefálico , Transtorno Depressivo Maior/diagnóstico por imagem , Emoções , Feminino , Humanos , Injeções Intravenosas , Ketamina/administração & dosagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Oxigênio/sangueRESUMO
OBJECTIVE: Symptom heterogeneity in major depressive disorder obscures diagnostic and treatment-responsive biomarker identification. Whether symptom constellations are differentially changed by electroconvulsive therapy (ECT) remains unknown. We investigate the clustering of depressive symptoms over the ECT index and whether ECT differentially influences symptom clusters. METHODS: The 17-item Hamilton Depression Rating Scale (HDRS-17) was collected from 111 patients with current depressive episode before and after ECT from 4 independent participating sites of the Global ECT-MRI Research Collaboration. Exploratory factor analysis of HDRS-17 items pre- and post-ECT treatment identified depressive symptom dimensions before and after ECT. A 2-way analysis of covariance was used to determine whether baseline symptom clusters were differentially changed by ECT between treatment remitters (defined as patients with posttreatment HDRS-17 total score ≤8) and nonremitters while controlling for pulse width, titration method, concurrent antidepressant treatment, use of benzodiazepine, and demographic variables. RESULTS: A 3-factor solution grouped pretreatment HDRS-17 items into core mood/anhedonia, somatic, and insomnia dimensions. A 2-factor solution best described the symptoms at posttreatment despite poorer separation of items. Among remitters, core mood/anhedonia symptoms were significantly more reduced than somatic and insomnia dimensions. No differences in symptom dimension trajectories were observed among nonremitting patients. CONCLUSIONS: Electroconvulsive therapy targets the underlying source of depressive symptomatology and may confer differential degrees of improvement in certain core depressive symptoms. Our findings of differential trajectories of symptom clusters over the ECT index might help related predictive biomarker studies to refine their approaches by identifying predictors of change along each latent symptom dimension.
Assuntos
Transtorno Depressivo Maior/psicologia , Transtorno Depressivo Maior/terapia , Transtorno Depressivo Resistente a Tratamento/psicologia , Transtorno Depressivo Resistente a Tratamento/terapia , Eletroconvulsoterapia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antidepressivos/uso terapêutico , Benzodiazepinas/uso terapêutico , Terapia Combinada , Análise Fatorial , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Resultado do TratamentoRESUMO
BACKGROUND: Clinical brain MRI is normal in the majority of patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. However, extensive deep white matter damage wasrecently identifiedin these patients using diffusion weighted imaging. Here, our aim was to study a particularly vulnerable brain compartment, the late myelinating superficial white matter. METHODS: Forty-six patients with anti-NMDAR encephalitis were included. Ten out of these were considered neurologically recovered (modified Rankin scale of zero), while 36 patients were non-recovered. In addition, 30 healthy controls were studied. MRI data were collected from all subjects and superficial white matter mean diffusivity derived from diffusion tensor imaging was compared between groups in whole brain, lobar and vertex-based analyses. Patients underwent comprehensive cognitive testing, and correlation analyses were performed between cognitive performance and superficial white matter integrity. RESULTS: Non-recovered patients showed widespread superficial white matter damage in comparison to recovered patients and healthy controls. Vertex-based analyses revealed that damage predominated in frontal and temporal lobes. In contrast, the superficial white matter was intact in recovered patients. Importantly, persistent cognitive impairments in working memory, verbal memory, visuospatial memory and attention significantly correlated with damage of the superficial white matter in patients. CONCLUSIONS: Anti-NMDAR encephalitis is associated with extensive superficial white matter damage in patients with incomplete recovery. The strong association with impairment in several cognitive domains highlights the clinical relevance of white matter damage in this disorder and warrants investigations of the underlying pathophysiological mechanisms.
Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato/patologia , Substância Branca/patologia , Adulto , Encefalite Antirreceptor de N-Metil-D-Aspartato/complicações , Estudos de Casos e Controles , Disfunção Cognitiva/complicações , Disfunção Cognitiva/patologia , Imagem de Tensor de Difusão , Feminino , Lobo Frontal/patologia , Humanos , Masculino , Neuroimagem , Indução de Remissão , Lobo Temporal/patologia , Adulto JovemRESUMO
BACKGROUND: Electroconvulsive therapy (ECT) is a highly effective brain stimulation treatment for severe depression. Identifying neurochemical changes linked with ECT may point to biomarkers and predictors of successful treatment response. METHODS: We used proton magnetic resonance spectroscopy (1H-MRS) to measure longitudinal changes in glutamate/glutamine (Glx), creatine (Cre), choline (Cho) and N-acetylaspartate (NAA) in the dorsal (dACC) and subgenual anterior cingulate cortex (sgACC) and bilateral hippocampus in patients receiving ECT scanned at baseline, after the second ECT session and after the ECT treatment series. Patients were compared with demographically similar controls at baseline. Controls were assessed twice to establish normative values and variance. RESULTS: We included 50 patients (mean age 43.78 ± 14 yr) and 33 controls (mean age 39.33 ± 12 yr) in our study. Patients underwent a mean of 9 ± 4.1 sessions of ECT. At baseline, patients showed reduced Glx in the sgACC, reduced NAA in the left hippocampus and increased Glx in the left hippocampus relative to controls. ECT was associated with significant increases in Cre in the dACC and sgACC and decreases in NAA in the dACC and right hippocampus. Lower NAA levels in the dACC at baseline predicted reductions in depressive symptoms. Both ECT and symptom improvement were associated with decreased Glx in the left hippocampus and increased Glx in the sgACC. LIMITATIONS: Attrition and clinical heterogeneity may have masked more subtle findings. CONCLUSION: ECT elicits robust effects on brain chemistry, impacting Cre, NAA and Glx, which suggests restorative and neurotrophic processes. Differential effects of Glx in the sgACC and hippocampus, which approach control values with treatment, may reflect previously implicated underactive cortical and overactive subcortical limbic circuitry in patients with major depression. NAA levels at baseline are predictive of therapeutic outcome and could inform future treatment strategies.
Assuntos
Transtorno Depressivo Maior/metabolismo , Transtorno Depressivo Maior/terapia , Eletroconvulsoterapia , Giro do Cíngulo/metabolismo , Hipocampo/metabolismo , Adulto , Biomarcadores/líquido cefalorraquidiano , Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/metabolismo , Transtorno Bipolar/terapia , Estudos Transversais , Transtorno Depressivo Maior/diagnóstico por imagem , Feminino , Seguimentos , Giro do Cíngulo/diagnóstico por imagem , Hipocampo/diagnóstico por imagem , Humanos , Estudos Longitudinais , Masculino , Espectroscopia de Prótons por Ressonância Magnética , Escalas de Graduação Psiquiátrica , Análise de Regressão , Resultado do TratamentoRESUMO
Major depressive disorder (MDD) is associated with dysfunctional corticolimbic networks, making functional connectivity studies integral for understanding the mechanisms underlying MDD pathophysiology and treatment. Resting-state functional connectivity (RSFC) studies analyze patterns of temporally coherent intrinsic brain activity in "resting-state networks" (RSNs). The default-mode network (DMN) has been of particular interest to depression research; however, a single RSN is unlikely to capture MDD pathophysiology in its entirety, and the DMN itself can be characterized by multiple RSNs. This, coupled with conflicting previous results, underscores the need for further research. Here, we measured RSFC in MDD by targeting RSNs overlapping with corticolimbic regions and further determined whether altered patterns of RSFC were restored with electroconvulsive therapy (ECT). MDD patients exhibited hyperconnectivity between ventral striatum (VS) and the ventral default-mode network (vDMN), while simultaneously demonstrating hypoconnectivity with the anterior DMN (aDMN). ECT influenced this pattern: VS-vDMN hyperconnectivity was significantly reduced while VS-aDMN hypoconnectivity only modestly improved. RSFC between the salience RSN and dorsomedial prefrontal cortex was also reduced in MDD, but was not affected by ECT. Taken together, our results support a model of ventral/dorsal imbalance in MDD and further suggest that the VS is a key structure contributing to this desynchronization.
RESUMO
Verbal and physical aggression begin early in life and steadily decline thereafter in normal development. As a result, elevated aggressive behavior in adolescence may signal atypical development and greater vulnerability for negative mental and health outcomes. Converging evidence suggests that brain disturbances in regions involved in impulse control, emotional regulation, and sensation seeking may contribute to heightened aggression. However, little is known regarding the neural mechanisms underlying subtypes of aggression (i.e., proactive and reactive aggression) and whether they differ between males and females. Using a sample of 106 14-year-old adolescent twins, this study found that striatal enlargement was associated with both proactive and reactive aggression. We also found that volumetric alterations in several frontal regions including smaller middle frontal and larger orbitofrontal cortex were correlated with higher levels of aggression in adolescent twins. In addition, cortical thickness analysis showed that thickness alterations in many overlapping regions including middle frontal, superior frontal, and anterior cingulate cortex and temporal regions were associated with aggression in adolescent twins. Results support the involvement of fronto-limbic-striatal circuit in the etiology of aggression during adolescence. Aggr. Behav. 43:230-240, 2017. © 2016 Wiley Periodicals, Inc.
Assuntos
Comportamento do Adolescente/fisiologia , Agressão/fisiologia , Córtex Cerebral/anatomia & histologia , Neostriado/anatomia & histologia , Adolescente , Feminino , Giro do Cíngulo/anatomia & histologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Lobo Occipital/anatomia & histologia , Córtex Pré-Frontal/anatomia & histologiaRESUMO
OBJECTIVES: The risk of cognitive impairment is a concern for patients with major depressive disorder receiving electroconvulsive therapy (ECT). Here, we evaluate the acute, short-term and long-term effects of ECT on tests of processing speed, executive function, memory, and attention. METHODS: Forty-four patients with major depressive disorder receiving ECT (61% right unilateral, 39% mixed right unilateral-bitemporal, left unilateral, and/or bitemporal lead placement) underwent a cognitive battery prior to ECT (T1), after 2 sessions (T2), and at the end of the index (T3). Thirty-two patients returned for a 6-month follow-up (T4). Thirty-three control subjects were assessed at 2 times approximately 4 weeks apart (C1 and C2). RESULTS: At baseline, patients showed deficits in processing speed, executive function, and memory compared with control subjects. Including depression severity and lead placement covariates, linear mixed-model analysis showed significant improvement in only processing speed between T1 and T3 and between T1 and T4 in patients. An acute decline in attention and verbal memory was observed at T2, but performance returned to baseline levels at T3. Longitudinal cognitive outcomes did not differ in patients defined as ECT responders/nonresponders. LIMITATIONS: Episodic memory was not measured, and medications were not controlled between T3 and T4. Control subjects also showed improvements in processing speed, suggesting practice effects for some measures. CONCLUSIONS: In this naturalistic ECT treatment study, results show that the initiation of ECT may transiently affect memory and executive function, but cognition is largely unaffected during and after ECT. Whereas some functions might improve, others will at least remain stable up to 6 months following the ECT index.
Assuntos
Cognição , Transtorno Depressivo Maior/psicologia , Transtorno Depressivo Maior/terapia , Eletroconvulsoterapia/efeitos adversos , Eletroconvulsoterapia/métodos , Eletroconvulsoterapia/psicologia , Adulto , Idoso , Atenção , Função Executiva , Feminino , Humanos , Masculino , Memória , Pessoa de Meia-Idade , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Recidiva , Resultado do TratamentoRESUMO
White matter abnormalities have been shown in the large deep fibers of Alzheimer's disease patients. However, the late myelinating superficial white matter comprised of intracortical myelin and short-range association fibers has not received much attention. To investigate this area, we extracted a surface corresponding to the superficial white matter beneath the cortex and then applied a cortical pattern-matching approach which allowed us to register and subsequently sample diffusivity along thousands of points at the interface between the gray matter and white matter in 44 patients with Alzheimer's disease (Age: 71.02 ± 5.84, 16M/28F) and 47 healthy controls (Age 69.23 ± 4.45, 19M/28F). In patients we found an overall increase in the axial and radial diffusivity across most of the superficial white matter (P < 0.001) with increases in diffusivity of more than 20% in the bilateral parahippocampal regions and the temporal and frontal lobes. Furthermore, diffusivity correlated with the cognitive deficits measured by the Mini-Mental State Examination scores (P < 0.001). The superficial white matter has a unique microstructure and is critical for the integration of multimodal information during brain maturation and aging. Here we show that there are major abnormalities in patients and the deterioration of these fibers relates to clinical symptoms in Alzheimer's disease.