The main result of the present study is that neurocognitive dysfunction in bipolar and schizophrenia spectrum disorders appears to be determined more by history of psychosis than by DSM-IV–defined diagnostic category or subtype.
Our first set of findings shows that while the bipolar group with a lifetime history of psychosis had neurocognitive dysfunction similar to that of the schizophrenia and schizoaffective disorder groups, the bipolar group without previous psychotic episodes had neurocognitive function similar to the normal controls, apart from in processing speed where they performed poorer. To our knowledge, this is the first time this has been shown in an adequately powered study comprising broad diagnostic groups assessed with the same clinical rating scales and a comprehensive neuropsychological test battery. Moreover, our findings reveal that the group mean differences in neurocognition have clinical significance, as severe impairment was more common in the groups with a history of psychosis. On average, clinically significant cognitive impairment occurred in approximately one-third with schizophrenia spectrum disorders, one-fourth with psychotic bipolar disorder, but only in one-tenth with nonpsychotic bipolar disorder.
Overall, this first set of findings, in which groups with a history of psychosis have more severe neurocognitive dysfunction than the bipolar group without a history of psychosis, is consistent with but expands on a line of previous findings.13–17,19,20
However, inconsistent with this overall picture yet consistent with some previous reports,13
we found poorer verbal memory and processing speed in schizophrenia compared with psychotic bipolar disorder. Furthermore, we found more severe impairment in the psychotic bipolar group compared with the nonpsychotic bipolar group across more measures (verbal fluency and interference control) than many previous studies, although, there is at least one previous report of poorer interference control in a psychotic compared with a nonpsychotic bipolar group.18
Our nonpsychotic bipolar group was only impaired in processing speed, which has been related to the clinical expression of bipolar disorder.33
Thus, unlike many previous studies, our nonpsychotic bipolar group was generally unimpaired. There are however reports of relatively intact neurocognitive function for nonpsychotic bipolar disorder in at least one earlier study.15
The present lack of impairment could be explained by the relatively small deficit effect sizes across our sample. Alternatively, the participants in this group may be impaired compared with their premorbid functioning despite performing above the normative seventh percentile level.
Because the psychotic bipolar group had more bipolar I participants and the nonpsychotic bipolar group had more bipolar II participants, there is partial overlap between history of psychosis and diagnostic subtype. Our second set of findings however revealed that history of psychosis explains the neurocognitive variance in the bipolar sample better than diagnostic subtype. History of psychosis had effect on most neurocognitive measures even when controlling for bipolar diagnostic subtype, while diagnostic subtype only had effect on the two verbal recall measures. This indicates that the difference in neurocognitive dysfunction between psychotic and nonpsychotic bipolar groups are not due to diagnostic subtype, ie, severity of elated states. Nevertheless, because psychosis can occur during either mania or depression in bipolar I and by definition only during phases of depression in bipolar II, psychosis may be qualitatively different in bipolar I and II participants. Therefore, we cannot rule out that the predominance of bipolar I in our psychotic bipolar group may have in some way influenced this group’s neurocognitive performance.
Overall, this second set of findings supports and expands on a recent study, which found that bipolar diagnostic subtype did not have significant influence on neurocognitive measures and thus could not explain the differences they found between psychotic and nonpsychotic bipolar groups.17
The current report of bipolar diagnostic subtype only influencing verbal recall measures is in line with our earlier report where bipolar I and II were only significantly different on verbal memory measures.6
A consistency in findings was expected as the first sample covers approximately half of the current bipolar sample.
Our follow-up analyses indicate that none of the demographic and clinical differences between groups can fully explain the group differences in neurocognition. Thus, it seems that the psychotic bipolar group is neurocognitively closer to the schizophrenia spectrum disorders, than to the nonpsychotic bipolar group. Firstly, and in line with previous reports,40
we found few differences in demographic and clinical characteristics between the psychotic and nonpsychotic bipolar groups. Secondly, although demographic variables were associated with neurocognitive function, group differences in neurocognitive performance remained significant despite controlling for gender, age, premorbid IQ, and education. Thirdly, in line with Glahn et al,19
we found few associations between neurocognitive and clinical measures. Associations were primarily found between neurocognition in the bipolar sample and number of psychotic episodes and hospitalizations, both of which are related to history of psychosis. Moreover, group differences in neurocognition remained significant despite controlling for all current symptom measures and in line with previous reports10
; current psychosis did not influence neurocognitive performance. Group differences also remained significant after controlling for all illness course variables.
Due to the study design, we cannot disentangle the effects of medications from the effect of illness severity causing medication use. As there was no difference between our groups in proportion with antidepressants and combination therapy, they were not considered likely confounders. The effects on neurocognition from antiepileptic medication are considered minimal41
and the effect of lithium unclear.42,43
Moreover, group differences in neurocognitive performance remained significant despite controlling for antiepileptic medication and lithium use; thus, these medications are not considered likely confounders. Because the use of antipsychotic medication naturally has a very high degree of association with a history of psychosis, it is impossible to disentangle their effect from that of history of psychosis. However, because most recent findings also seem to indicate, if any, an improved cognitive function associated with typical as well as atypical antipsychotic medication,44,45
we do not find it likely that the use of antipsychotics explains our main findings. Finally, because all group differences remained significant after excluding clinical participants with substance abuse last 6 months from the analyses, we argue that substance abuse last 6 months cannot explain our main findings.
The present findings have several implications. Firstly, they imply that future neurocognitive research needs to study individuals with bipolar disorder with a history of psychosis separately from those without. Secondly, in line with neuroimaging and genetic studies,46,47
they indicate that individuals with a history of psychosis might share common neurobiological substrates across the major DSM-IV
schizophrenia and bipolar spectrum distinctions. Thus, in line with recent reports,33,48
this suggests neurocognition as an endophenotypic marker for these disorders. We argue that our findings support a more dimensional view of mental disorders in line with that of Vieta and Phillips,1
proposing that future diagnostic systems should incorporate dimensional consideration of a range of clinical symptoms beyond those of the primary symptom that determines main category belonging and that psychotic symptoms should be part of the diagnostic criteria for bipolar disorder.
The main limitation of the present study is that not all diagnostic participants were asymptomatic. Because we might be less likely to find differences between these groups during symptomatic phases,13
we might find differences between the 3 groups with a history of psychosis in an entirely remitted sample. That the psychotic bipolar group had more participants with bipolar I disorder than the nonpsychotic bipolar group may be considered a limitation. But as it is in line with other samples,17
it may in fact represent subtype-specific differences. Finally, future studies should examine whether neurocognitive dysfunction is related to type or severity of psychotic history, including whether there is a difference between mood-congruent and mood-incongruent psychosis, between psychosis during mania and psychosis during depression, or between hallucinations and delusions.49
In conclusion, neurocognitive dysfunction in bipolar and schizophrenia spectrum disorders seems to be more related to history of psychosis than to DSM-IV–defined diagnostic category or subtype. From a neurocognitive point of view, this suggests that the major diagnostic distinction between disorders that are predominantly psychotic and predominantly affective is too simplistic, supporting a more dimensional approach in future diagnostic systems.