Subthreshold conditions as precursors for full syndrome disorders: a 15-year longitudinal study of multiple diagnostic classes.

Since the advent of well-specified psychiatric diagnostic systems, such as the DSM’s 1980 3rd revision, reliability of diagnoses has greatly improved as has the precision of prevalence rates. These systems employ specific thresholds for determining ‘caseness’ but, recently, interest in studying subthreshold conditions (i.e., slightly below the threshold) has increased (Pincus, McQueen, & Elinson, 2003). This work is especially important because subthreshold conditions are common (Lewinsohn, Shankman, Gau & Klein, 2004), and are associated with functional impairment (Kessler, Zhao, Blazer, & Swartz, 1997) Studying subthreshold conditions can help determine whether full syndromes (FS) are qualitatively different from conditions below diagnostic thresholds or whether they are merely more severe forms on a continuum (Flett, Vredenburg, & Krames, 1997; Lewinsohn, Solomon, Steeley, & Zeiss, 2000a). Among subthreshold conditions, subthreshold depression has been studied the most extensively. Subthreshold depressive conditions, such as minor depression or Brief Recurrent Depression, have been associated with significant impairment (Gotlib, Lewinsohn, & Seeley, 1995; Kessler et al., 1997), and increased treatment utilization (Judd, Paulus, Wells & Rapaport, 1996). Similar results have been found for subthreshold bipolar (Lewinsohn, Klein & Seeley, 2000b), anxiety (Batelaan, De Graaf, Van Balkom, Vollebergh, & Beekman, 2007), and alcohol and substance use disorders (Pollock & Martin, 1999). The clinical significance and validity of subthreshold conditions can be addressed with several different methods (Robins & Guze, 1970). Cross-sectional studies can establish the prevalence of subthreshold conditions and whether they are associated with impairment. Family studies can elucidate whether FS and subthreshold conditions are associated with qualitatively distinct familial liabilities. Using data from the Oregon Adolescent Depression Project (OADP), we have begun to examine these questions (Lewinsohn et al., 2004; Shankman, Klein, Lewinsohn, Seeley & Small, 2008). In this paper, we will extend these studies by examining the prospective course of subthreshold conditions. Specifically, we will examine whether subthreshold conditions are likely to develop or escalate into FS disorders. Subthreshold depression (Fergusson, Horwood, Ridder & Beautrais, 2005; Lewinsohn et al., 2000a) bipolar disorder (Lewinsohn et al, 2000b; Regeer et al., 2006) and anxiety disorder (Merikangas et al., 2003) have been shown to escalate into the FS condition over time. These and similar studies have led many to argue that subthreshold conditions may be precursors of the FS (Eaton, Badawi & Melton, 1995, Pincus et al., 2003). Most subthreshold studies only examine whether a single subthreshold condition is likely to develop into the FS form of that disorder over time (i.e., homotypic development). Equally important, however, is whether subthreshold conditions predict the development of other FS disorders over time (i.e., heterotypic development), as heterotypic developments can elucidate whether subthreshold conditions are precursors to broad classes of psychopathologies. With the possible exception of MDD and bipolar disorder, heterotypic developments have been largely ignored in the subthreshold literature (Lewinsohn et al., 2000b; Regeer et al., 2006). We predict that, in addition to homotypic escalation, several subthreshold conditions will develop into heterotypic FS disorders, as there is substantial comorbidity and familial co-aggregation among subthreshold and FS conditions (Angst, Merikangas & Preisig, 1997; Lewinsohn et al., 2004; Shankman et al., 2008). Given the phenotypic and genotypic clustering of psychopathologies into broad classes of internalizing and externalizing disorders (Kendler, Prescott, Myers, & Neale, 2003; Krueger & Markon, 2006), we expect that subthreshold internalizing disorders such as depression and anxiety will escalate into FS forms of each other (Fergusson et al., 2005), and subthreshold externalizing disorders such as alcohol, substance, and conduct /antisocial personality disorder (ASPD) will escalate into FS forms of one another (Hicks et al., 2007). It is also possible that externalizing subthreshold conditions may escalate into internalizing conditions given recent support (Kim-Cohen et al., 2003), though these findings are less likely than within class escalation.