The present report estimated the long-term (i.e. 10-year) consistency of a bipolar diagnosis among first-admission respondents hospitalized with psychosis early in the course of their illness. It represents one of the first studies to examine multiple factors, particularly childhood factors, that could help explain lack of consistency in the bipolar diagnosis across time. The major findings indicated that among respondents who were diagnosed at least once with bipolar disorder across a 10 year period, only half (50.3%) were consistently given this diagnosis at every available assessment. Correlates of inconsistency included greater number of psychiatric symptoms, more psychotic symptoms, worse overall functioning, and presenting after a depressive or mixed episode versus a manic one. Childhood factors associated with diagnostic inconsistency included childhood psychopathology and worse premorbid functioning in adolescence.
The results can be understood in two ways. On the one hand, almost 80% of the cohort diagnosed at baseline with bipolar disorder retained this diagnosis at the 10 year follow-up, indicating that many cases of bipolar disorder can be reliably diagnosed from an early point in treatment. These estimates of prospective consistency are higher than those found in other studies (8
), highlighting how a comprehensive assessment relying on multiple sources of information can reduce diagnostic uncertainty.
On the other hand, only half of the respondents (50.3%) who were ever diagnosed with bipolar disorder were consistently given this diagnosis across the 10 years, that is received the diagnosis at every assessment. So while many respondents have a clear presentation with little diagnostic ambiguity, almost half are diagnostically confusing at some point, even in a research setting where diagnostic practices are more comprehensive than those in routine clinical care. Such a proportion is not insignificant, raising the question of what led to this uncertainty.
One explanation may be that some respondents initially manifested affective symptoms with psychosis but suffered from a different illness. The latter only became clearer over time as their symptoms evolved, with psychotic symptoms becoming more temporally prominent and their functioning declining markedly. This appears to have been the case for at least a third of the inconsistently diagnosed respondents (e.g., cases 4–5 in ). Many of them were initially diagnosed with bipolar disorder, but over the course of 10 years, their features had become more consistent with the diagnosis of a schizoaffective disorder or schizophrenia. Some may argue that some of these respondents, particularly those with schizoaffective disorder, manic subtype, are part of the bipolar spectrum (40
) and therefore not different from those who were more consistently diagnosed. This is a theoretical issue, but it is important to note that in the present sample, respondents who were given a schizoaffective diagnosis had developed clear symptoms of schizophrenia, though there remained occasional episodes of mania or depression superimposed. The development of negative symptoms and increased prominence of psychotic symptoms were also reflected in their lowered functioning over the follow-up. Therefore, this was not simply a poorer bipolar outcome group but the development of a different condition from bipolar disorder.
A second explanation for the diagnostic uncertainty among the inconsistently diagnosed respondents was that they had not yet manifested clear signs of bipolar disorder at baseline, resulting in a diagnostic shift later in the study. Indeed, many of the latter group were initially diagnosed with major depressive disorder or had an unknown diagnosis; most of these individuals were re-diagnosed with bipolar disorder because their symptom picture had changed or become clearer (e.g., cases 1–3 in ). These findings highlight the need for early diagnoses among patients originally presenting with psychosis to be conceptualized as provisional until the course of the disorder makes the diagnosis clearer. While data specifically pertaining to MDD with psychosis are not the focus of the present report, it is important to note that most people with this diagnosis did not go on to develop bipolar disorder (11
This left about 16% of the sample with a random diagnostic pattern that could not be easily grouped. They demonstrated a complex interplay of developmental, behavioral, substance abuse and clinical symptoms that made mania and depression criteria difficult to apply and interpret consistently.
In comparing respondents who were inconsistently diagnosed with bipolar disorder to those who were consistently diagnosed, we found that the latter group was more likely to have had a manic episode and to have been identified by their treating physician as having bipolar disorder at the time of their initial admission. This again suggests that for many respondents, a correct diagnosis is obvious at early stages of treatment. Conversely, respondents with an unstable diagnostic picture tended to have more complex psychiatric symptoms, including a greater number of psychotic symptoms, which most likely reflected the confusion between schizophrenia spectrum disorder and bipolar disorder.
With respect to childhood factors, respondents with evidence of childhood psychopathology and poorer premorbid functioning beginning in early adolescence were much more likely to be inconsistently diagnosed. How these childhood variables affected the diagnostic picture is not entirely clear. Part of their effects on diagnosis may be mediated by worse global functioning prior to the initial baseline assessment, which may have led to a more complex clinical presentation. Alternatively, childhood behavior problems may have represented early manifestations of schizophrenia; indeed, behavior problems and poor premorbid adjustment are known to be associated with schizophrenia outcomes (41
). If so, some of these respondents may have had a schizophrenia spectrum disorder that was confused with bipolar disorder initially, resulting in inconsistent diagnoses in adulthood.
Other variables that we hypothesized would distinguish between consistently and inconsistently diagnosed respondents were non-significant, including the presence of mixed symptoms at times other than the initial presentation. Substance abuse was common in the entire sample but was not associated with more diagnostic inconsistency. Its severity was not analyzed for this report, however, and future studies might consider whether severity of substance abuse is a distinguishing factor.
Findings may also have implications for the validity of our current psychiatric nosology as well for diagnostic guidelines for patients hospitalized with psychotic symptoms. Clearly, a large subset of patients have a stable diagnostic course over time, suggesting that our bipolar I disorder construct is valid (at least with regard to course). However, an equally large number of patients had an unstable diagnostic path. For many patients, diagnostic uncertainty diminished over the follow-up. These findings suggest that, short of presenting with an uncomplicated manic episode, longitudinal clarification of symptoms may be necessary before confidently establishing a bipolar diagnosis at least among patients whose initial hospitalization involves psychosis. Given that comorbidity with childhood-onset behavior disorders occurred more frequently in participants with unstable diagnoses, circumspection for their diagnosis might be especially warranted.
Findings from this study must be viewed within the context of its limitations. Among these, results are based on a group of primarily bipolar I manic patients initially hospitalized with psychosis, which may limit generalizability. This limitation is offset in part by significant benefits of this recruitment approach: Salvtore and colleagues (44
) note that first-episode follow-up studies like the current one are less likely to be confounded by the effects of recruiting from settings where patients may be in later stages of their illness. As a result, the current sample is less likely to be confounded by the effects of chronic illness, disability, institutionalization, and changes produced from years of treatment (44
). The analysis was also limited by the presence of some missing data, as well as the fact that the impact of Axis II psychopathology was not considered. The missing data limitation was mitigated by two factors. First, attrition was remarkably small for a study of this length. Second, missingness was not related to our primary outcomes, providing no evidence that dropping out was related to the consistency or inconsistency of a bipolar diagnosis. Lastly, although the clinicians responsible for consensus diagnosis were blind to previous research diagnoses, interviewers performing the SCID interviews were aware of prior SCID diagnoses. We would suggest, however, that this would lead to greater diagnostic consistency rather than the pattern found here.
In summary, in one of the longest studies to ever follow people with bipolar disorder, the diagnosis was found to be highly variable. Half were consistently given the diagnosis across a 10-year period involving four research assessments. Yet for the other half, the phenomenology was not sufficiently clear to provide long-term diagnostic consistency even when using state of the art assessments and expert diagnosticians. Several studies have noted that a number of years elapse before the correct diagnosis of bipolar disorder is made, with some suggesting that part of the reason for the delay may be a neglect to carefully screen for bipolar disorder (e.g., 45
). The present study makes clear that even with optimal assessment practices, diagnosing bipolar disorder early and consistently over the long-term remains a major challenge.