RESUMO
BACKGROUND: Pathological worry is a hallmark feature of generalised anxiety disorder (GAD), associated with dysfunctional emotional processing. The ventromedial prefrontal cortex (vmPFC) is involved in the regulation of such processes, but the link between vmPFC emotional responses and pathological v. adaptive worry has not yet been examined.AimsTo study the association between worry and vmPFC activity evoked by the processing of learned safety and threat signals. METHOD: In total, 27 unmedicated patients with GAD and 56 healthy controls (HC) underwent a differential fear conditioning paradigm during functional magnetic resonance imaging. RESULTS: Compared to HC, the GAD group demonstrated reduced vmPFC activation to safety signals and no safety-threat processing differentiation. This response was positively correlated with worry severity in GAD, whereas the same variables showed a negative and weak correlation in HC. CONCLUSIONS: Poor vmPFC safety-threat differentiation might characterise GAD, and its distinctive association with GAD worries suggests a neural-based qualitative difference between healthy and pathological worries.Declaration of interestNone.
Assuntos
Transtornos de Ansiedade/fisiopatologia , Ansiedade/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Adolescente , Adulto , Ansiedade/psicologia , Transtornos de Ansiedade/psicologia , Mapeamento Encefálico/métodos , Estudos de Casos e Controles , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Adulto JovemRESUMO
OBJECTIVE: The question of how to best conceptualize health anxiety (HA) from a diagnostic and etiological perspective remains debated. The aim was to examine the relationship between HA and the symptoms of anxiety and obsessive-compulsive-related disorders in a normative twin population. METHOD: Four hundred and ninety-six monozygotic adult twin pairs from the Australian Twin Registry participated in the study (age, 34.4 ± 7.72 years; 59% females). Validated scales were used to assess each domain. We applied a twin regression methodology-ICE FALCON-to determine whether there was evidence consistent with 'causal' relationships between HA and other symptoms by fitting and comparing model estimates. RESULTS: Estimates were consistent with higher levels of obsessing ('unwanted thoughts') (P = 0.008), social anxiety (P = 0.03), and body dysmorphic symptoms (P = 0.008) causing higher levels of HA symptoms, and with higher levels of HA symptoms causing higher levels of physical/somatic anxiety symptoms (P = 0.001). CONCLUSION: Obsessional thoughts, body dysmorphic concerns, and social anxiety symptoms may have a causal influence on HA. To report physical/somatic anxiety appears to be a consequence of the underlying presence of HA-related fears. Should our results be confirmed by longitudinal studies, the evaluation and treatment of HA may benefit from the consideration of these identified risk factors.
Assuntos
Transtornos de Ansiedade/epidemiologia , Atitude Frente a Saúde , Transtornos Dismórficos Corporais/epidemiologia , Hipocondríase/epidemiologia , Transtorno Obsessivo-Compulsivo/epidemiologia , Sistema de Registros/estatística & dados numéricos , Adolescente , Adulto , Austrália/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Fobia Social/epidemiologia , Gêmeos Monozigóticos , Adulto JovemRESUMO
Classical Pavlovian fear conditioning remains the most widely employed experimental model of fear and anxiety, and continues to inform contemporary pathophysiological accounts of clinical anxiety disorders. Despite its widespread application in human and animal studies, the neurobiological basis of fear conditioning remains only partially understood. Here we provide a comprehensive meta-analysis of human fear-conditioning studies carried out with functional magnetic resonance imaging (fMRI), yielding a pooled sample of 677 participants from 27 independent studies. As a distinguishing feature of this meta-analysis, original statistical brain maps were obtained from the authors of 13 of these studies. Our primary analyses demonstrate that human fear conditioning is associated with a consistent and robust pattern of neural activation across a hypothesized genuine network of brain regions resembling existing anatomical descriptions of the 'central autonomic-interoceptive network'. This finding is discussed with a particular emphasis on the neural substrates of conscious fear processing. Our associated meta-analysis of functional deactivations-a scarcely addressed dynamic in fMRI fear-conditioning studies-also suggests the existence of a coordinated brain response potentially underlying the 'safety signal' (that is, non-threat) processing. We attempt to provide an integrated summary on these findings with the view that they may inform ongoing studies of fear-conditioning processes both in healthy and clinical populations, as investigated with neuroimaging and other experimental approaches.
Assuntos
Encéfalo/fisiologia , Condicionamento Clássico/fisiologia , Medo/fisiologia , Adulto , Ansiedade/fisiopatologia , Transtornos de Ansiedade/fisiopatologia , Mapeamento Encefálico , Feminino , Giro do Cíngulo/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , MasculinoRESUMO
BACKGROUND: Negative mood states are composed of symptoms of depression and anxiety, and by a third factor related to stress, tension and irritability. We sought to clarify the nature of the relationships between the factors by studying twin pairs. METHOD: A total of 503 monozygotic twin pairs completed the Depression Anxiety Stress Scales (DASS), an instrument that assesses symptoms of depression, anxiety and stress-tension. We applied a recently developed twin regression methodology - Inference about Causation from Examination of FAmiliaL CONfounding (ICE FALCON) - to test for evidence consistent with the existence of 'causal' influences between the DASS factors. RESULTS: There was evidence consistent with the stress-tension factor having a causal influence on both the depression (p < 0.0001) and anxiety factors (p = 0.001), and for the depression factor having a causal influence on the anxiety factor (p < 0.001). CONCLUSIONS: Our findings suggest a critical role for stress-tension in the structure of negative mood states, and that interventions that target it may be particularly effective in reducing depression and anxiety symptoms.
Assuntos
Ansiedade/psicologia , Depressão/psicologia , Estresse Psicológico/psicologia , Adulto , Causalidade , Feminino , Humanos , Masculino , Gêmeos MonozigóticosRESUMO
BACKGROUND: The amygdala and subgenual anterior cingulate cortex (sACC) are key brain regions for the generation of negative affect. In this longitudinal fMRI study of adolescents we investigated how amygdala-sACC connectivity was correlated with negative affectivity (NA) both cross-sectionally and longitudinally, and examined its relationship to the onset of first-episode depression. METHOD: Fifty-six adolescents who were part of a larger longitudinal study of adolescent development were included. They had no history of mental illness at the time of their baseline scan (mean age 16.5 years) and had a follow-up scan 2 years later (mean age 18.8 years). We used resting-state functional-connectivity MRI to investigate whether cross-sectional and change measures of amygdala-sACC connectivity were (i) correlated with NA and its change over time, and (ii) related to the onset of first-episode depression. RESULTS: The magnitude of amygdala connectivity with sACC showed significant positive correlation with NA at both time-points. Further analysis confirmed that change in amygdala-sACC connectivity between assessments was correlated with change in NA. Eight participants developed a first episode of depression between the baseline and follow-up assessments: they showed increased amygdala-sACC connectivity at follow-up. CONCLUSIONS: Amygdala-sACC connectivity is associated with NA in adolescence, with change in connectivity between these regions showing positive correlation with change in NA. Our observation that the onset of depression was associated with an increase in connectivity between the regions provides support for the neurobiological 'scar' hypothesis of depression.
Assuntos
Afeto , Tonsila do Cerebelo/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Giro do Cíngulo/fisiopatologia , Adolescente , Encéfalo/fisiopatologia , Estudos de Coortes , Estudos Transversais , Feminino , Neuroimagem Funcional , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/fisiopatologia , Lobo Parietal/fisiopatologia , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Imaging for pre-operative localisation of parathyroid glands in primary hyperparathyroidism is now routine. This has led to the detection of incidental lesions (incidentalomas) in other organs, the nature of which is not well characterised. The aim of this study was to determine the incidence, characteristics and outcomes in patients who had incidental findings on parathyroid imaging. METHODS: Records of patients who underwent imaging for primary hyperparathyroidism over 2 years were reviewed to identify incidental lesions detected on parathyroid imaging. Patients with persistent or renal hyperparathyroidism were excluded. Details on the management of detected incidentalomas were obtained from patient records. RESULTS: Incidentalomas were identified in 17 of 170 patients (10%) undergoing parathyroid imaging. Incidentalomas included thyroid (n = 11), breast (n = 3), lateral compartment of the neck (n = 1), lung (n = 1) and clavicle (n = 1). However, no disease of clinical significance needing treatment was detected on further investigation. CONCLUSIONS: Although a significant proportion of patients undergoing parathyroid imaging had incidental lesions detected, these seem to be of little clinical significance. The morbidity and cost of further interventions on these incidentalomas need to be weighed against the benefits of routine imaging in improving outcomes of first-time surgery in patients with primary hyperparathyroidism.
Assuntos
Neoplasias da Mama/diagnóstico , Hiperparatireoidismo Primário/diagnóstico , Achados Incidentais , Imagem Multimodal/métodos , Neoplasias das Paratireoides/diagnóstico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/cirurgia , Feminino , Seguimentos , Humanos , Hiperparatireoidismo Primário/metabolismo , Hiperparatireoidismo Primário/cirurgia , Masculino , Pessoa de Meia-Idade , Neoplasias das Paratireoides/metabolismo , Neoplasias das Paratireoides/cirurgia , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Preoperative imaging in patients undergoing surgery for primary hyperparathyroidism (PHPT) is used primarily to facilitate targeted parathyroidectomy. Failure of preoperative localisation mandates a bilateral exploration. It is thought that the results of imaging may also predict the success of surgery. The aims of this study were to assess whether the findings on preoperative localisation influenced outcomes following parathyroidectomy for PHPT and to explore factors underlying failure to cure at surgery. METHODS: We analysed outcomes of all patients who underwent first-time surgery for PHPT in two centres over a 5-year period to determine an association with demographic characteristics and findings on preoperative imaging. Records of patients not cured by initial surgery were reviewed to explore factors underlying failure to cure. RESULTS: The failure rate (persistent disease) in the entire cohort was 5 % (25/541) (bilateral neck explorations, 5 %; unilateral exploration, 7 %; targeted approach, 4 %), while two patients developed recurrent disease. In patients who had undergone dual imaging with an ultrasound scan and (99m)Tc-sestamibi scintigraphy, failure rates with "lateralised and concordant" imaging, "nonconcordant" imaging, and "dual-negative" imaging were 2, 9, and 11 %, respectively (p = 0.01). Of the 25 patients with persistent disease, multigland disease (MGD) was present in 52 % (13/25) and ectopic adenoma in 24 % (6/12). CONCLUSIONS: Patients with PHPT who do not have lateralised and concordant dual imaging are at higher risk of persistent disease. A significant proportion of failures are due to the inability to recognise the presence and/or extent of MGD.
Assuntos
Hiperparatireoidismo Primário/cirurgia , Paratireoidectomia , Cuidados Pré-Operatórios , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hiperparatireoidismo Primário/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Cintilografia , Falha de Tratamento , UltrassonografiaRESUMO
PURPOSE: Sentinel node biopsy (SNB) may identify lymph node metastases in patients with papillary thyroid cancer (PTC), enabling selective application of central node dissection (CND). The aim of this study was to assess the feasibility of implementing SNB in patients undergoing thyroidectomy for a cytologically indeterminate/suspicious/malignant thyroid nodule and to determine the potential improvement in clinical outcomes and the costs associated with the SNB technique. METHODS: The treatment strategies and clinical and pathological outcomes of two retrospective cohorts of patients who underwent preoperative thyroid FNA over a 5-year period in two different centres were studied. The potential for implementing the SNB technique and the benefits and costs associated with implementation were estimated. RESULTS: In centre 1, in 819 adult patients who had thyroid fine-needle aspiration cytology, the final cytology was indeterminate, suspicious and diagnostic of malignancy in 113, 29 and 28 patients, respectively. One hundred eight patients were 'suitable' for SNB. Twenty-three of these patients had PTC, six of whom underwent CND. Of these six patients, node metastasis was absent in five--the cohort in whom prophylactic CND may have been avoided consequent to a negative 'sentinel node' biopsy. Morbidity attributable to CND may have been avoided in up to four patients over a 5-year period. Costs associated with implementation of SNB outweighed any potential savings. Analysis of 491 patients in centre 2 confirmed that the benefit of SNB in PTC was similarly limited; morbidity attributable to CND may have been avoided in up to seven patients over a 5-year period. CONCLUSIONS: Even under ideal conditions (assuming 100 % node identification rate and 0 % false negative rate), the potential short- to medium-term benefit of sentinel node biopsy in patients with thyroid cancer in centres implementing a policy of selective or routine prophylactic CND is low.
Assuntos
Carcinoma/patologia , Metástase Linfática/patologia , Biópsia de Linfonodo Sentinela , Neoplasias da Glândula Tireoide/patologia , Adulto , Carcinoma/economia , Carcinoma/cirurgia , Carcinoma Papilar , Estudos de Coortes , Análise Custo-Benefício/economia , Inglaterra , Estudos de Viabilidade , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Esvaziamento Cervical/economia , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela/economia , Medicina Estatal/economia , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/economia , Neoplasias da Glândula Tireoide/cirurgia , Nódulo da Glândula Tireoide/economia , Nódulo da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/cirurgia , Tireoidectomia/economiaRESUMO
BACKGROUND: There is evidence to suggest that cognitive deficits might persist beyond the acute stages of illness in major depressive disorder (MDD). However, the findings are somewhat inconsistent across the individual studies conducted to date. Our aim was to conduct a systematic review and meta-analysis of existing studies that have examined cognition in euthymic MDD patients. METHOD: Following a systematic search across several publication databases, meta-analyses were conducted for 27 empirical studies that compared euthymic adult MDD patients (895 participants) and healthy controls (997 participants) across a range of cognitive domains. The influence of demographic variables and confounding factors, including age of onset and recurrent episodes, was examined. RESULTS: Compared with healthy controls, euthymic MDD patients were characterized by significantly poorer cognitive functions. However, the magnitude of observed deficits, with the exception of inhibitory control, were generally modest when late-onset cases were excuded. Late-onset cases demonstrated significantly more pronounced deficits in verbal memory, speed of information processing and some executive functions. CONCLUSIONS: Cognitive deficits, especially poor response inhibition, are likely to be persistent features, at least of some forms, of adult-onset MDD. More studies are necessary to examine cognitive dysfunction in remitted psychotic, melancholic and bipolar spectrum MDD. Cognitive deficits overall appear to be more common among patients with late-onset depression, supporting the theories suggesting that possible vascular and neurodegenerative factors play a role in a substantial number of these patients.
Assuntos
Transtornos Cognitivos/etiologia , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/classificação , HumanosRESUMO
BACKGROUND: Distorted images of the observable self are considered crucial in the development and maintenance of social anxiety. We generated an experimental situation in which participants viewed themselves from an observer's perspective when exposed to scrutiny and evaluation by others. Method Twenty patients with social anxiety disorder (SAD) and 20 control subjects were assessed using functional magnetic resonance imaging (fMRI) during the public exposure of pre-recorded videos in which they were each shown performing a verbal task. The examiners acted as the audience in the experiment and rated performance. Whole-brain functional maps were computed using Statistical Parametric Mapping. RESULTS: Robust activation was observed in regions related to self-face recognition, emotional response and general arousal in both study groups. Patients showed significantly greater activation only in the primary visual cortex. By contrast, they showed significant deactivation or smaller activation in dorsal frontoparietal and anterior cingulate cortices relevant to the cognitive control of negative emotion. Task-related anxiety ratings revealed a pattern of negative correlation with activation in this frontoparietal/cingulate network. Importantly, the relationship between social anxiety scores and neural response showed an inverted-U function with positive correlations in the lower score range and negative correlations in the higher range. CONCLUSIONS: Our findings suggest that exposure to scrutiny and evaluation in SAD may be associated with changes in cortical systems mediating the cognitive components of anxiety. Disorder severity seems to be relevant in shaping the neural response pattern, which is distinctively characterized by a reduced cortical response in the most severe cases.
Assuntos
Transtornos de Ansiedade/fisiopatologia , Mapeamento Encefálico , Córtex Cerebral/fisiopatologia , Emoções/fisiologia , Autoimagem , Adolescente , Adulto , Transtornos de Ansiedade/psicologia , Nível de Alerta/fisiologia , Estudos de Casos e Controles , Face , Feminino , Frequência Cardíaca/fisiologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Reconhecimento Psicológico/fisiologia , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUND: Patients with bipolar disorder (BD) frequently suffer from neurocognitive deficits that can persist during periods of clinical stability. Specifically, impairments in executive functioning such as working memory and in self-processing have been identified as the main components of the neurocognitive profile observed in euthymic BD patients. The study of the neurobiological correlates of these state-independent alterations may be a prerequisite to develop reliable biomarkers in BD. METHODS: A sample of 27 euthymic BD patients and 25 healthy participants (HC) completed working memory and self-referential functional Magnetic Resonance Imaging (fMRI) tasks. Activation maps obtained for each group and contrast images (i.e., 2-back > 1-back/self > control) were used for comparisons between patients and HC. RESULTS: Euthymic BD patients, in comparison to HC, showed a higher ventromedial prefrontal cortex activation during working memory, a result driven by the lack of deactivation in BD patients. In addition, euthymic BD patients displayed a greater dorsomedial and dorsolateral prefrontal cortex activation during self-reference processing. LIMITATIONS: Pharmacotherapy was described but not included as a confounder in our models. Sample size was modest. CONCLUSION: Our findings revealed a lack of deactivation in the anterior default mode network (aDMN) during a working memory task, a finding consistent with prior research in BD patients, but also a higher activation in frontal regions within the central executive network (CEN) during self-processing. These results suggest that an imbalance of neural network dynamics underlying external/internal oriented cognition (the CEN and the aDMN, respectively) may be one of the first reliable biomarkers in euthymic bipolar patients.
Assuntos
Transtorno Bipolar , Humanos , Transtorno Bipolar/tratamento farmacológico , Memória de Curto Prazo/fisiologia , Encéfalo , Transtorno Ciclotímico , Imageamento por Ressonância Magnética , BiomarcadoresRESUMO
BACKGROUND: Methylene blue is an intraoperative adjunct for localization of enlarged parathyroid glands. The availability of preoperative and other intraoperative localization methods, and the reported adverse effects of methylene blue make its routine use debatable. The aim of this study was to perform a systematic review of the use of methylene blue in parathyroidectomy. METHODS: A systematic review of English-language literature in MEDLINE and Scopus databases on the use of intravenous methylene blue in parathyroid surgery was carried out. RESULTS: There were no randomized clinical trials. Thirty-nine observational studies were identified, of which 33 did not have a control arm. The overall median staining rate for abnormal parathyroid glands was 100 per cent. The median cure rates in the methylene blue and no-methylene blue arms were 100 and 98 per cent respectively. Neurotoxicity was reported in 25 patients, all of whom were taking serotonergic medication. CONCLUSION: Observational evidence suggests that methylene blue is efficacious in identifying enlarged parathyroid glands. Toxicity appears to be mild in the absence of concomitant use of serotonin reuptake inhibitors. The effectiveness of methylene blue in the context of currently used preoperative and intraoperative localization techniques has yet to be shown.
Assuntos
Corantes , Azul de Metileno , Doenças das Paratireoides/cirurgia , Paratireoidectomia/métodos , Corantes/administração & dosagem , Corantes/efeitos adversos , Reações Falso-Positivas , Humanos , Infusões Intravenosas , Azul de Metileno/administração & dosagem , Azul de Metileno/efeitos adversos , Duração da Cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Depression has been associated with functional alterations in several areas of the cingulate cortex. In this study we have taken a systematic approach to examining how alterations in functional connectivity vary across the functionally diverse subregions of the rostral cingulate cortex. Method Eighteen patients with major depressive disorder, aged 15 to 24 years, were matched with 20 healthy control participants. Using resting-state functional connectivity magnetic resonance imaging (fcMRI), we systematically investigated the functional connectivity of four subregions of the rostral cingulate cortex. Voxelwise statistical maps of each subregion's connectivity with other brain areas were compared between the patient and control groups. RESULTS: The depressed participants showed altered patterns of connectivity with ventral cingulate subregions. They showed increased connectivity between subgenual anterior cingulate cortex (ACC) and dorsomedial frontal cortex, with connectivity strength showing positive correlation with illness severity. Depressed participants also showed increased connectivity between pregenual ACC and left dorsolateral frontal cortex, and decreased connectivity between pregenual ACC and the caudate nucleus bilaterally. CONCLUSIONS: The results reinforce the importance of subgenual ACC for depression, and show a close link between brain regions that support self-related processes and affective visceromotor function. The pregenual ACC also has an important role, with its increased connectivity with dorsolateral frontal cortex suggesting heightened cognitive regulation of affect; and reduced connectivity with the caudate nucleus potentially underlying symptoms such as anhedonia, reduced motivation and psychomotor dysfunction.
Assuntos
Encéfalo/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Giro do Cíngulo/fisiopatologia , Adolescente , Estudos de Casos e Controles , Núcleo Caudado/fisiopatologia , Feminino , Lobo Frontal/fisiopatologia , Neuroimagem Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/fisiopatologia , Adulto JovemRESUMO
BACKGROUND: Abnormalities in cortico-striatal-pallidal-thalamic (CSPT) circuits have been implicated in major depressive disorder (MDD). However, the robustness of these findings across studies is unclear, as is the extent to which they are influenced by demographic, clinical and pharmacological factors. METHOD: With the aim of clarifying these questions, we conducted a meta-analysis to map the volumetric abnormalities that were most robustly identified in CSPT circuits of individuals with MDD. A systematic search identified 41 studies meeting our inclusion criteria. RESULTS: There were significant volume reductions in prefrontal (especially orbitofrontal) and anterior cingulate cortices, and also in subcortical structures such as the caudate nucleus and putamen, with effect sizes ranging from small to moderate. The subgenual anterior cingulate and orbitofrontal cortices were significantly smaller in antidepressant-free samples compared to medicated patients. Late-life depression (LLD) tended to be associated with smaller volumes in circumscribed frontal and subcortical structures, with the most robust differences being found in thalamic volume. CONCLUSIONS: Individuals with major depression demonstrate volumetric abnormalities of CSPT circuits. However, these observations may be restricted to certain subgroups, highlighting the clinical heterogeneity of the disorder. On the basis of this meta-analysis, CSPT abnormalities were more prominent in those with LLD whereas antidepressant use seemed to normalize certain cortical volumetric abnormalities.
Assuntos
Encéfalo/patologia , Transtorno Depressivo Maior/patologia , Fatores Etários , Gânglios da Base , Encéfalo/fisiopatologia , Mapeamento Encefálico , Grupos Controle , Interpretação Estatística de Dados , Transtorno Depressivo Maior/fisiopatologia , Giro do Cíngulo , Humanos , Imageamento por Ressonância Magnética , Córtex Pré-Frontal , Análise de Regressão , Índice de Gravidade de Doença , TálamoRESUMO
BACKGROUND: Sentinel node biopsy (SNB) is employed as standard treatment in some solid organ cancers to assess lymph node spread and enable targeted treatment. Several studies have investigated the role of SNB in thyroid cancer. This is a systematic review and meta-analysis of the role of SNB in the management of thyroid cancer. METHODS: A systematic search was performed in the PubMed database to identify all original articles on the role of SNB in thyroid cancer. Data on methodologies used, short-term outcomes and adverse effects were summarized, and used to address relevant clinical questions related to the application of the SNB technique in thyroid cancer. RESULTS: Twenty-four studies were included. The overall sentinel node (SN) detection rates for the blue dye, radioisotope and combined techniques were 83·7, 98·4 and 96 per cent respectively. A positive SN was seen in 42·9 per cent of patients with papillary thyroid cancer with an identified SN. The overall false-negative rates for the blue dye, radioisotope and combined techniques were 7·7, 16 and 0 per cent respectively. A negative frozen-section examination of the SN was unreliable in 12·0 per cent of patients. Immunohistochemical assessment of the SN showed evidence of nodal metastases in an additional 15 per cent of patients (7 of 47 sentinel nodes). CONCLUSION: SNB in thyroid cancer is a promising technique that has the potential to avoid prophylactic lymph node surgery in up to 57 per cent of patients with clinically node-negative thyroid cancer.
Assuntos
Biópsia de Linfonodo Sentinela/métodos , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Carcinoma , Carcinoma Papilar , Humanos , Metástase Linfática , Estudos Prospectivos , Estudos Retrospectivos , Sensibilidade e Especificidade , Biópsia de Linfonodo Sentinela/efeitos adversos , Câncer Papilífero da TireoideRESUMO
BACKGROUND: Fetal akinesia deformation sequence syndrome (FADS) is a heterogeneous disorder characterised by fetal akinesia and developmental defects including, in some case, pterygia. Multiple pterygium syndromes (MPS) are traditionally divided into prenatally lethal and non-lethal (such as Escobar) types. Previously, we and others reported that homozygous mutations in the fetal acetylcholine receptor gamma subunit (CHRNG) can cause both lethal and non-lethal MPS, demonstrating that pterygia resulted from fetal akinesia, and that mutations in the acetylcholine receptor subunits CHRNA1, CHRND, and Rapsyn (RAPSN) can also result in a MPS/FADS phenotype. METHODS: We hypothesised that mutations in other acetylcholine receptor related genes may interfere with neurotransmission at the neuromuscular junction and so we analysed 14 cases of lethal MPS/FADS without CHRNG, CHRNA1, CHRNB1, CHRND, or RAPSN mutations for mutations in DOK7. RESULTS: A homozygous DOK7 splice site mutation, c.331+1G>T, was identified in a family with three children affected with lethal FADS. Previously DOK7 mutations have been reported to underlie a congenital myaesthenic syndrome with a characteristic "limb girdle" pattern of muscle weakness. CONCLUSION: This finding is consistent with the hypothesis that whereas incomplete loss of DOK7 function may cause congenital myasthenia, more severe loss of function can result in a lethal fetal akinesia phenotype.
Assuntos
Anormalidades Múltiplas/genética , Mutação em Linhagem Germinativa , Proteínas Musculares/genética , Anormalidades Múltiplas/patologia , Processamento Alternativo/genética , Sequência de Bases , Criança , Consanguinidade , Análise Mutacional de DNA , Deficiências do Desenvolvimento/patologia , Feminino , Humanos , Índia , Masculino , Sítios de Splice de RNA/genética , SíndromeRESUMO
Both clinicians and neuroscientists have been long interested in the topic of fear conditioning, with recent advances in neuroscience, in particular, igniting a shared interest in further translation between these domains. Here, we review some historical aspects of this relationship and the progress that has been made in translating the neuroscientific study of fear conditioning to the conceptualization and treatment of mental disorders, especially anxiety-related disorders. We also address some conceptual and methodological challenges faced by this research, and offer some suggestions to support future progress in the field.
Assuntos
Ansiedade/psicologia , Condicionamento Psicológico/fisiologia , Medo/psicologia , Humanos , NeurociênciasRESUMO
BACKGROUND: Current brain-based theoretical models of generalized anxiety disorder (GAD) suggest a dysfunction of amygdala-ventromedial prefrontal cortex emotional regulatory mechanisms. These alterations might be reflected by an altered resting state functional connectivity between both areas and could extend to vulnerable non-clinical samples such as high worriers without a GAD diagnosis. However, there is a lack of information in this regard. METHODS: We investigated differences in resting state functional connectivity between the basolateral amygdala and the ventromedial prefrontal cortex (amygdala-vmPFC) in 28 unmedicated participants with GAD, 28 high-worriers and 28 low-worriers. We additionally explored selected clinical variables as predictors of amygdala-vmPFC connectivity, including anxiety sensitivity. RESULTS: GAD participants presented higher left amygdala-vmPFC connectivity compared to both groups of non-GAD participants, and there were no differences between the latter two groups. In our exploratory analyses, concerns about the cognitive consequences of anxiety (the cognitive dimension of anxiety sensitivity) were found to be a significant predictor of the left amygdala-vmPFC connectivity. LIMITATIONS: The cross-sectional nature of our study preclude us from assessing if functional connectivity measures and anxiety sensitivity scores entail an increased risk of GAD. CONCLUSIONS: These results suggest a neurobiological qualitative distinction at the level of the amygdala-vmPFC emotional-regulatory system in GAD compared to non-GAD participants, either high- or low-worriers. At this neural level, they question previous hypotheses of continuity between high worries and GAD development. Instead, other anxiety traits such as anxiety sensitivity might confer a greater proneness to the amygdala-vmPFC connectivity alterations observed in GAD.
Assuntos
Transtornos de Ansiedade , Imageamento por Ressonância Magnética , Tonsila do Cerebelo/diagnóstico por imagem , Ansiedade/diagnóstico por imagem , Transtornos de Ansiedade/diagnóstico por imagem , Estudos Transversais , Humanos , Córtex Pré-Frontal/diagnóstico por imagemRESUMO
BACKGROUND: Social anxiety often involves a combination of hypervigilance and avoidance to potentially warning signals including the facial expression of emotions. Functional imaging has demonstrated an increase in amygdala response to emotional faces in subjects with social anxiety. Nevertheless, it is unclear to what extent visual areas processing faces influence amygdala reactivity in different socially anxious individuals. We assessed the influence of the fusiform gyrus activation on amygdala response to emotional faces in the non-clinical range of social anxiety. METHOD: Twenty-two normal subjects showing a wide range in social anxiety scores were examined using functional magnetic resonance imaging (fMRI) during the processing of happy and fearful faces. A dimensional analysis approach was used involving voxel-wise mapping of the correlation between subjects' social anxiety scores and amygdala activation, before and after controlling for fusiform gyrus activation. RESULTS: We observed that only after controlling for subjects' level of activation of the fusiform gyrus was there an association between social anxiety ratings and amygdala response to both happy and fearful faces. The fusiform gyrus influence was more robust during the fear condition. Of note, fusiform gyrus response to fearful faces showed a negative correlation with additional behavioral assessments related to avoidance, including social anxiety scores, harm avoidance and sensitivity to punishment. CONCLUSIONS: Relevant interactions among the emotional face-processing stages exist in the non-clinical range of social anxiety that may ultimately attenuate amygdala responses. Future research will help to establish the role of this effect in a clinical context.