Anxiety sensitivity predicts depression severity in individuals with dissociative identity disorder.

BACKGROUND: Anxiety sensitivity involves the fear of anxiety-related symptoms and can exacerbate both major depressive disorder and posttraumatic stress disorder (PTSD) symptoms. However, it is unclear if anxiety sensitivity plays a similar role in dissociative identity disorder (DID) where symptoms of depression and PTSD commonly co-occur. We examined the association between anxiety sensitivity, depression, PTSD and dissociative symptoms in DID, hypothesizing a positive association between all symptoms and anxiety sensitivity. METHOD: Participants were 21 treatment-seeking adult females with histories of childhood trauma, current PTSD, and DID. Participants completed the Anxiety Sensitivity Index (ASI), Beck Depression Inventory-II, Childhood Trauma Questionnaire, Multidimensional Inventory of Dissociation, and PTSD Checklist for DSM-5. The ASI included subscales that assessed anxiety sensitivity in cognitive, physical, and social domains. RESULTS: Participants reported high levels of anxiety sensitivity. A multiple regression analysis demonstrated that the ASI cognitive subscale was the strongest predictor of depressive symptoms. No direct associations were identified between anxiety sensitivity and PTSD or dissociative symptoms. We conducted a mediation analysis to test an indirect relationship between cognitive anxiety sensitivity and dissociative symptoms, and found a significant indirect effect through depressive symptoms. CONCLUSIONS: Our results suggest that cognitive anxiety sensitivity or the fear of cognitive dyscontrol is linked with symptom severity in DID. These findings emphasize the need to assess for and utilize interventions that target anxiety sensitivity, which may in turn alleviate symptoms of depression and dissociation in DID.

Modulating the dysregulated migration of pulmonary arterial hypertensive smooth muscle cells with motif mimicking cell permeable peptides.

Migration of vascular smooth muscle cells is a key element in remodeling during pulmonary arterial hypertension (PAH). We are observing key alterations in the migratory characteristics of human pulmonary artery smooth muscle cells (HPASMC) isolated from transplanted lungs of subjects with PAH. Using wound migration and barrier removal assays, we demonstrate that the PAH cells migrate under quiescent growth conditions and in the absence of pro-migratory factors such as platelet derived growth factor (PDGF). Under the same conditions, in the absence of PDGF, non-PAH HPASMC show negligible migration. The dysregulated migration initiates, in part, through phosphorylation events signaled through the unstimulated PDGF receptor via focal adhesion kinase (FAK) whose total basal expression and phosphorylation at tyrosine 391 is markedly increased in the PAH cells and is inhibited by a motif mimicking cell-permeable peptide (MMCPP) targeting the Tyr751 region of the PDGF receptor and by imatinib. However, exposure of the PAH cells to PDGF further promotes migration. Inhibition of p21 activated kinases (PAK), LIM kinases (LIMK), c-Jun N-terminal kinases (JNK) and p38 mitogen-activated protein kinases (MAPK) reduces both the dysregulated and the PDGF-stimulated migration. Immunofluorescence microscopy confirms these observations showing activated JNK and p38 MAPK at the edge of the wound but not in the rest of the culture in the PAH cells. The upstream inhibitors FAK (PF-573228) and imatinib block this activation of JNK and p38 at the edge of the site of injury and correspondingly inhibit migration. MMCPP which inhibit the activation of downstream effectors of migration, cofilin and caldesmon, also limit the dysregulated migration. These results highlight key pathways which point to potential targets for future therapies of pulmonary hypertension with MMCPP.