RESUMEN
Obsessive-compulsive disorder (OCD), like other illnesses with prominent anxiety, may involve abnormal fear regulation and consolidation of safety memories. Impaired fear extinction memory (extinction recall, ER) has been shown in individuals with current symptoms of OCD [1]. However, contrary to expectations, the only previous study investigating this phenomenon showed a positive correlation between extinction recall abilities and OCD symptomology (i.e., as OCD symptoms worsened, extinction memory improved). The purpose of the current study was to determine if patients with a lifetime diagnosis of OCD (not necessarily currently symptomatic) also demonstrate impairments in extinction memory, and the relationship between OCD symptomology and extinction memory in this type of sample. In addition, we also examined fear renewal, which has never been investigated in an OCD sample. We enrolled 37 patients with OCD, the majority of whom were on serotonin reuptake inhibitors, and 18 healthy control participants in a 2-day paradigm assessing fear conditioning and extinction (Day 1) and extinction retention and renewal (Day 2). Skin conductance responses (SCRs) were the dependent measure. Results, as in the prior study, indicated that the only between-group difference was impaired ER in OCD patients relative to controls. Contrary to our prediction, OCD symptom severity was not correlated with the magnitude of extinction recall. There were no differences in fear renewal between OCD patients and controls.
Asunto(s)
Condicionamiento Psicológico , Extinción Psicológica , Miedo , Memoria , Trastorno Obsesivo Compulsivo/psicología , Adolescente , Adulto , Anciano , Electrochoque , Femenino , Respuesta Galvánica de la Piel , Mano , Humanos , Masculino , Persona de Mediana Edad , Trastorno Obsesivo Compulsivo/tratamiento farmacológico , Trastorno Obsesivo Compulsivo/fisiopatología , Escalas de Valoración Psiquiátrica , Pruebas Psicológicas , Psicofísica , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Adulto JovenRESUMEN
Laminin and elastin, two major constituents of the extracellular matrix, bind to cells via the elastin-laminin receptor (ELR), a receptor distinct from integrins. Despite the ubiquitous nature of elastin and laminin in the matrix, the consequences of activation of the ELR are unknown. Because integrins are capable of mechanosensitive transduction, we hypothesized that the ELR would exert a similar function. Accordingly, we examined the effects of cyclical stretch on canine coronary smooth muscle gene expression and proliferation that are mediated by the ELR. Northern blot analyses showed a 31% decrease in serum-induced expression of c-fos when cells were stretched for 30 min on elastin, but no change in expression was observed on collagen. Serum-induced proliferation of stretched cells was markedly attenuated on elastin when compared with collagen. Both the molecular (decreased c-fos expression) and biological (decreased proliferation) responses on elastin were restored after blockade of the ELR with the elastin fragment hexapeptide (valine-glycine-valine-alanine-proline-glycine, VGVAPG). The inhibition was specific for this peptide, as another hydrophobic hexapeptide (valine-serine-leucine-serine-proline-glycine, VSLSPG) did not inhibit the responses. These results demonstrate that cyclic stretch inhibits c-fos expression and proliferation of coronary vascular smooth muscle cells grown on elastin matrixes, a mechanosensitive response that is transduced by the ELR.