RESUMEN
Prospective clinical studies support a link between psychological stress and multiple sclerosis (MS) disease severity, and peripheral stress systems are frequently dysregulated in MS patients. However, the exact link between neurobiological stress systems and MS symptoms is unknown. To evaluate the link between neural stress responses and disease parameters, we used an arterial-spin-labeling functional MRI stress paradigm in 36 MS patients and 21 healthy controls. Specifically, we measured brain activity during a mental arithmetic paradigm with performance-adaptive task frequency and performance feedback and related this activity to disease parameters. Across all participants, stress increased heart rate, perceived stress, and neural activity in the visual, cerebellar and insular cortex areas compared with a resting condition. None of these responses was related to cognitive load (task frequency). Consistently, although performance and cognitive load were lower in patients than in controls, stress responses did not differ between groups. Insula activity elevated during stress compared with rest was negatively linked to impairment of pyramidal and cerebral functions in patients. Cerebellar activation was related negatively to gray matter (GM) atrophy (i.e., positively to GM volume) in patients. Interestingly, this link was also observed in overlapping areas in controls. Cognitive load did not contribute to these associations. The results show that our task induced psychological stress independent of cognitive load. Moreover, stress-induced brain activity reflects clinical disability in MS. Finally, the link between stress-induced activity and GM volume in patients and controls in overlapping areas suggests that this link cannot be caused by the disease alone.
Asunto(s)
Encéfalo/patología , Evaluación de la Discapacidad , Esclerosis Múltiple/patología , Esclerosis Múltiple/psicología , Estrés Psicológico/patología , Atrofia , Mapeo Encefálico , Cognición , Demografía , Femenino , Sustancia Gris/patología , Frecuencia Cardíaca/fisiología , Humanos , Hidrocortisona/metabolismo , Imagen por Resonancia Magnética , Masculino , Matemática , Persona de Mediana Edad , Tamaño de los Órganos , Saliva/metabolismo , Estrés Psicológico/complicaciones , Análisis y Desempeño de Tareas , Sustancia Blanca/patologíaRESUMEN
BACKGROUND: The hippocampus is likely involved in mood disorders, but in vivo evidence for the role of anatomically distinct hippocampal subregions is lacking. Multiple sclerosis, an inflammatory disease of the central nervous system, is linked to a high prevalence of depression as well as hippocampal damage and may thus provide important insight into the pathologic correlates of medical depression. We examined the role of subregional hippocampal volume for depression in relapsing-remitting multiple sclerosis. METHODS: Anatomically defined hippocampal subregional volumes (cornu ammonis 1-3 [CA1-CA3] and the dentate gyrus [CA23DG], subiculum, entorhinal cortex) were measured using a high-resolution T2-weighted magnetic resonance imaging sequence in 29 relapsing-remitting multiple sclerosis patients and 20 matched healthy control subjects. Diurnal salivary cortisol was assessed at awakening, 4 pm, and 9 pm on 2 consecutive days. Subjects also completed the Beck Depression Inventory. RESULTS: Multiple sclerosis patients showed smaller hippocampal volumes compared with control subjects, particularly in the CA1 and subiculum subregions. In addition, multiple sclerosis patients with depressive symptoms (Beck Depression Inventory score >13) also showed smaller CA23DG volumes and higher cortisol levels. Within the multiple sclerosis group, CA23DG volume was correlated with depressive symptoms and cortisol levels. There were no associations with number of previous steroid treatments, global atrophy, or disease duration. CONCLUSIONS: This report provides in vivo evidence for selective association of smaller CA23DG subregional volumes in the hippocampus with cortisol hypersecretion and depressive symptoms in multiple sclerosis.