The aim of the present study was to investigate the relationship between treatment delay and excessive substance use. A total of 151 bipolar disorder (BD) I and II patients were consecutively recruited from in- and outpatient psychiatric units, and categorized as primary or secondary BD (without or with antecedent excessive substance use). Predictors of treatment delay among all patients, and predictors of subsequent excessive substance use among primary BD patients, were investigated with logistic regression analyses. The median treatment delay was 2.0 years (IQR 14.0). The risk of long treatment delays was increased in patients with BD II disorder, no lifetime psychosis, a higher age at first contact with specialized psychiatric services, primary BD, and excessive substance use. In primary BD, the risk for developing excessive substance use was increased in males, in patients with shorter education and longer treatment delays. Patients with antecedent excessive substance use had reduced risk of long treatment delays. The risk of developing excessive substance use after BD onset increased with longer treatment delays.

A single amino acid mutation (G156S) in the putative pore-forming region of the G protein-sensitive, inwardly rectifying K(+) channel subunit, GIRK2, renders the conductance constitutively active and nonselective for monovalent cations. The mutant channel subunit (GIRK2wv) causes the pleiotropic weaver disease in mice, which is characterized by the selective vulnerability of cerebellar granule cells and Purkinje cells, as well as dopaminergic neurons in the mesencephalon, to cell death. It has been proposed that divalent cation permeability through constitutively active GIRK2wv channels contributes to a rise in internal calcium in the GIRK2wv-expressing neurons, eventually leading to cell death. We carried out comparative studies of recombinant GIRK2wv channels expressed in Xenopus oocytes and COS-7 cells to determine the magnitude and relative permeability of the GIRK2wv conductance to Ca(2+). Data from these studies demonstrate that the properties of the expressed current differ in the two systems and that when recombinant GIRK2wv is expressed in mammalian cells it is impermeable to Ca(2+).