Alpha2 macroglobulin elevation without an acute phase response in depressed adults with Down's syndrome:: implications

Studies of immune function during depression in persons without intellectual disability (ID) have revealed elevated levels of alpha (2) macroglobulin (alpha M-2) and an acute phase protein (APP) response. Clinical observation suggests that people with Down's syndrome (DS) may have associated genetic abnormalities in their immune systems. The APP response and alpha M-2 changes in depressed versus non-depressed adults with DS was the subject of the present study. The serum pan-proteinase inhibitor alpha M-2, and the AP proteins c-reactive protein (CRP),alpha (1) antitrypsin (alpha (1)AT), ceruroplasmin (Cp), beta (2) Macroglobulin (beta M-2) transthyretin (Trans), serum amyloid protein (SAP), and albumin (Alb) were measured in 38 adults with DS, 19 of whom were diagnosed with and 19 without depression using a sandwich enzyme-linked immunosorbent assay (ELISA).The DSM-IV criteria were used for diagnoses. Medical and neurological examinations excluded medical disorders associated with APP response. Only alpha M-2 and CRP were significantly different in the depressed versus nondepressed groups. The alpha M-2 was higher, a response similar to one observed in depressed people without ID,but the CRP was lower in the depressed group, especially in those subjects not on psychotropic medications, contrary to the expected APP response to depression. The results suggest that alpha M-2 elevation in depressed adults with DS is independent of the APP response. An alternative explanation for its elevation is proposed linking the core symptom of depression with the mammalian dormancy/ hibernation process. Further studies are needed to confirm that alpha M-2 elevation is specific to depression and that it might provide a helpful marker for the diagnosis of depression in people with ID.