In conclusion, currently available research evidence supports the usefulness of some “psychosis” specifier in the diagnosis of major depression. This specifier should be kept separate from the “severity” one. It should be possible to record the presence of both mood-congruent and mood-incongruent psychotic features in the same patient. More precise guidelines should be provided about how to distinguish psychotic from nonpsychotic experiences (eg, delusional from nondelusional guilt and hallucinations from illusions). These should highlight how persistent experiences need to be in order to justify a label of psychosis. Some biological findings could be acknowledged in the “Associated laboratory findings” section of the DSM, but the diagnostic criteria should be based on the clinical picture.
There are a number of research areas that could help address the needs laid out for psychotic depression categorization. First, it would be important to consider the definition of psychosis in the context of major depression. Does the definition need to be broadened to include cognitive distortions, not just full delusions? What are the primary delusions that occur in PMD? How should these be defined and what distortions are commonly seen in the context of MDD?
Formal thought disorder in severely depressed patients is understudied. The BPRS conceptual disorganization item is perhaps not optimal to explore this disorder because it is framed on the formal thought disorder of schizophrenia and is but one item. One characteristic of the formal thought disorder of depressed patients is that, contrary to what is assumed by the BPRS, its quality is not necessarily reflected by the degree of verbal production. For instance, a severely depressed patient with crowded or racing thoughts will often have a reduced (rather than increased) verbal production based on the nature of the mood component. Thus, we do not know whether, to what extent, or how formal thought disorder is manifest in major depression nor do we know its relationship to formal thought disorder in schizophrenia. More specific research in this area is warranted.
The DSM-IV distinction between mood-congruent and mood-incongruent psychotic symptoms in depressed patients makes intuitive sense. However, there is little specific evidence for this distinction or its relevance. It would be helpful to gather more data on the prevelance and importance of mood congruence in relation to prognosis, course, and outcome. Other issues to be investigated include: does having mood-incongruent psychotic symptoms put one at greater risk for relapse or a manic episode? Do those with mood-congruent psychotic symptoms have a better outcome than those with mood-incongruent symptoms?
A second important area of research is to develop a short neurocognitive battery that could help differentiate PMD from NPMD. Neuorcognitive batteries can be very complex and time consuming, and these would not be of benefit within a typical clinical practice. However, if a short battery could be developed to differentiate these patients with adequate sensitivity and specificity, it would be a very useful clinical tool. Starting with the neuropsychological findings to date, executive functioning, verbal memory, and psychomotor speed are the 3 areas which consistently are found to be impaired in PMDs. Issues that remain as problematic within the neuropsychology of PMD is that there are relatively few studies and medication status can be a factor.
A third issue for further study is whether any of the clinical, cognitive, or biological variables discussed above have diagnostic or prognostic value for psychotic depression. For example, do any of the specific psychotic or cognitive symptoms predict future PMD episodes or time to remission in the current episode? We already know that the presence of delusions and hallucinations in depressed patients does have some prognostic implications. Does the severity of the depressive episode (mild, moderate, or severe) also play a role in outcome? Psychotic episodes tend to have a longer duration and the recurrence rate tends to be higher. However, the medium- and long-term prognostic implications are less clear. In several studies, there was no significant difference in the outcome at 7 or 10 years between depressed patients with mood-congruent psychotic symptoms and nonpsychotic depressives. This may be in part due to the fact, reported by Winokur et al,73
that psychotic symptoms tend to become less prominent late in the course of the illness. This finding, however, requires replication.
In addition, data suggest that the presence of delusions and hallucinations in depressed patients has therapeutic implications. Depressed patients with mood-congruent delusions and hallucinations are less likely to respond to antidepressant monotherapy than nonpsychotic depressives, but this is largely based on the tricyclic literature. However, the Italian data are highly suggestive of a potential benefit with SSRI monotherapy. This requires further controlled data.
There is some overlap between unipolar psychotic depression and bipolar disorder. A family history of bipolar disorder is significantly more frequent in depressed patients with mood-congruent psychotic symptoms than in nonpsychotic depressives, and we found that the percentage of patients with at least 2 manic symptoms in their index episode was significantly higher in the former.18
The prognostic and therapeutic implications of these findings should be further explored. Data on the familiality of psychotic depression is also needed to better understand genetic influences. Furthermore, we do not have adequate data on cognitive and biological overlap of PMD and bipolar disorder, and this may warrant further investigation. Last, the clinical, biological, and treatment differentiation between PMD and schizoaffective disorder (depressed type) needs further study as well.