RESUMO
BACKGROUND: Electroconvulsive therapy (ECT) is one of the most effective treatments for severe depression. However, little is known regarding brain functional processes mediating ECT effects. METHOD: In a non-randomized prospective study, functional magnetic resonance imaging data during the automatic processing of subliminally presented emotional faces were obtained twice, about 6 weeks apart, in patients with major depressive disorder (MDD) before and after treatment with ECT (ECT, n = 24). Additionally, a control sample of MDD patients treated solely with pharmacotherapy (MED, n = 23) and a healthy control sample (HC, n = 22) were obtained. RESULTS: Before therapy, both patient groups equally showed elevated amygdala reactivity to sad faces compared with HC. After treatment, a decrease in amygdala activity to negative stimuli was discerned in both patient samples indicating a normalization of amygdala function, suggesting mechanisms potentially unspecific for ECT. Moreover, a decrease in amygdala activity to sad faces was associated with symptomatic improvements in the ECT sample (r spearman = -0.48, p = 0.044), and by tendency also for the MED sample (r spearman = -0.38, p = 0.098). However, we did not find any significant association between pre-treatment amygdala function to emotional stimuli and individual symptom improvement, neither for the ECT sample, nor for the MED sample. CONCLUSIONS: In sum, the present study provides first results regarding functional changes in emotion processing due to ECT treatment using a longitudinal design, thus validating and extending our knowledge gained from previous treatment studies. A limitation was that ECT patients received concurrent medication treatment.
Assuntos
Tonsila do Cerebelo/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/terapia , Eletroconvulsoterapia/métodos , Imageamento por Ressonância Magnética/métodos , Avaliação de Resultados em Cuidados de Saúde , Adulto , Tonsila do Cerebelo/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Expressão Facial , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Genetic and neuroimaging research has identified neurobiological correlates of obesity. However, evidence for an integrated model of genetic risk and brain structural alterations in the pathophysiology of obesity is still absent. Here we investigated the relationship between polygenic risk for obesity, gray matter structure and body mass index (BMI) by the use of univariate and multivariate analyses in two large, independent cohorts (n=330 and n=347). Higher BMI and higher polygenic risk for obesity were significantly associated with medial prefrontal gray matter decrease, and prefrontal gray matter was further shown to significantly mediate the effect of polygenic risk for obesity on BMI in both samples. Building on this, the successful individualized prediction of BMI by means of multivariate pattern classification algorithms trained on whole-brain imaging data and external validations in the second cohort points to potential clinical applications of this imaging trait marker.
Assuntos
Substância Cinzenta/anatomia & histologia , Substância Cinzenta/fisiologia , Obesidade/genética , Córtex Pré-Frontal/anatomia & histologia , Córtex Pré-Frontal/fisiologia , Adulto , Algoritmos , Índice de Massa Corporal , Mapeamento Encefálico/métodos , Feminino , Predisposição Genética para Doença , Substância Cinzenta/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Obesidade/etiologia , Obesidade/patologia , Córtex Pré-Frontal/diagnóstico por imagem , Fatores de RiscoRESUMO
Tumour necrosis factor alpha (TNFα) has been implicated in the pathophysiology of neurodegenerative and neuropsychiatric disease, with research highlighting a role for TNFα in hippocampal and striatal regulation. TNFα signals are primarily transduced by TNF receptors 1 and 2 (TNFR1 and TNFR2), encoded by TNFRSF1A and TNFRSF1B, which exert opposing effects on cell survival (TNFR1, neurodegenerative; TNFR2, neuroprotective). We therefore sought to explore the respective roles of TNFR1 and TNFR2 in the regulation of hippocampal and striatal morphology in an imaging genetics study. Voxel-based morphometry was used to analyse the associations between TNFRSF1A (rs4149576 and rs4149577) and TNFRSF1B (rs1061624) genotypes and grey matter structure. The final samples comprised a total of 505 subjects (mean age = 33.29, SD = 11.55 years; 285 females and 220 males) for morphometric analyses of rs1061624 and rs4149576, and 493 subjects for rs4149577 (mean age = 33.20, SD = 11.56 years; 281 females and 212 males). Analyses of TNFRSF1A single nucleotide polymorphisms (SNPs) rs4149576 and rs4149577 showed highly significant genotypic associations with striatal volume but not the hippocampus. Specifically, for rs4149576, G homozygotes were associated with reduced caudate nucleus volumes relative to A homozygotes and heterozygotes, whereas for rs4149577, reduced caudate volumes were observed in C homozygotes relative to T homozygotes and heterozygotes. Analysis of the TNFRSF1B SNP rs1061624 yielded a significant association with hippocampal but not with striatal volume, whereby G homozygotes were associated with increased volumes relative to A homozygotes and heterozygotes. Our findings indicate a role for TNFR1 in regulating striatal but not hippocampal morphology, as well as a complementary role for TNFR2 in hippocampal but not in striatal morphology.
Assuntos
Corpo Estriado/fisiologia , Substância Cinzenta/fisiologia , Hipocampo/fisiologia , Receptores Tipo II do Fator de Necrose Tumoral/genética , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Adulto , Corpo Estriado/metabolismo , Feminino , Substância Cinzenta/metabolismo , Hipocampo/metabolismo , Humanos , Masculino , Neostriado/metabolismo , Polimorfismo de Nucleotídeo Único , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Receptores Tipo II do Fator de Necrose Tumoral/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Neuroimaging traits of either familial or environmental risk for major depressive disorder (MDD) have been interpreted as possibly useful vulnerability markers. However, the simultaneous occurrence of familial and environmental risk might prove to be a major obstacle in the attempt of recent studies to confine the precise impact of each of these conditions on brain structure. Moreover, the exclusive use of group-level analyses does not permit prediction of individual illness risk which would be the basic requirement for the clinical application of imaging vulnerability markers. Hence, we aimed to distinguish between brain structural characteristics of familial predisposition and environmental stress by using both group- and individual-level analyses. METHOD: We investigated grey matter alterations between 20 healthy control subjects (HC) and 20 MDD patients; 16 healthy first-degree relatives of MDD patients (FH+) and 20 healthy subjects exposed to former childhood maltreatment (CM+) by using a combined VBM/pattern recognition approach. RESULTS: We found similar grey matter reductions in the insula and the orbitofrontal cortex in patients and FH+ subjects and in the hippocampus in patients and CM+ subjects. No direct overlap in grey matter alterations was found between FH+ and CM+ subjects. Pattern classification successfully detected subjects at risk for the disease even by strictly focusing on morphological traits of MDD. CONCLUSIONS: Familial and environmental risk factors for MDD are associated with differing morphometric anomalies. Pattern recognition might be a promising instrument in the search for and future application of vulnerability markers for MDD.