One of the most controversial topics for the DSM-V committee is whether to include a new diagnosis called Risk Syndrome for First Psychosis. Patients with schizophrenia commonly report a history of prodromal symptoms before developing the full-blown disorder. Over the past couple of decades, researchers have tried to identify such “prodromal” patients before they declare themselves as psychotic, in the hopes that we might be able to prevent the disorder from manifesting by starting treatment at the first signs of a problem.

It’s a reasonable idea, but there are two problems. First, the data to prove that we can accurately identify future psychotics are not particularly convincing. Second, there is no clear evidence that initiating early treatment does much to improve the course of the psychosis.

The largest study to date relevant to this topic was the North American Prodrome Longitudinal Study, the results of which were published in early 2008 in the Archives of General Psychiatry (Canon TD et al., Arch Gen Psychiatry 2008;65:28-37). In this multisite study, 291 patients were identified as being at “high clinical risk” for psychosis, and they were observed naturalistically for an average of 2 ½ years. The conversion rate to psychosis was 35% over the 2 ½ years. Slightly over half of these converted patients ended up with schizophrenia spectrum diagnoses; the others had affective psychoses or psychosis NOS.

There has been much disagreement about how to interpret these findings. The authors were bullish, concluding that “these findings demonstrate that prospective ascertainment of individuals at risk for psychosis is feasible….” (See the Schizophrenia Research Forum website at http://bit.ly/6m6YMB for an engaging debate.) The problem with the 35% conversion rate is that 65% of high risk patients did not convert over the 2 ½ year period, and the steadily decreasing rate of conversion in that study implies that most never would convert. On the other hand, these “false positive” patients were still quite symptomatic and would likely have been in psychiatric care anyway. The unanswered question is whether giving these patients the loaded diagnosis “risk syndrome for first psychosis” might harm them. For example, the label “psychosis” might follow them throughout their lives, causing discrimination or poor self esteem. One can also argue that the diagnosis would ultimately help these patients by making them more insurable and eligible for intensive psychiatric treatment.

From a clinical standpoint, what are the implications of aggressively identifying patients who are at high risk for psychosis? Is there any evidence that early identification of psychosis enhances treatment? Unfortunately, not much. The most recent review of the early intervention literature found three relevant randomized clinical trials in which high risk patients were assigned to antipsychotic meds and/or cognitive behavioral therapy as opposed to a control arm of observation with no treatment. There was a significant early effect of treatment in these trials, but at one to four years of follow up, treatment lost any effect. In other words, treating not-yet psychotic patients may delay the onset of psychosis by a few months but it does not appear to prevent the eventual appearance of psychosis, nor does it moderate the severity of psychosis once it appears (de Koning MB et al., Acta Psychiatr Scand 2009;119:426-442).

Overall, it appears that the Risk Syndrome for Psychosis is an interesting diagnosis but requires more study to be convincing. We recommend that the DSM committee put the disorder in the appendix for now, and promote it to a full-fledged diagnosis as stronger evidence emerges.
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Proposed Criteria for Risk Syndrome for First Psychosis
All six of the following:

A. Characteristic Symptoms: At least one of the first three A criteria symptoms for Schizophrenia (delusions, hallucinations, disorganized speech) is present in attenuated form (attenuated positive symptoms). The symptom must be of sufficient severity and frequency as to be beyond the usual normal variation. Reality testing must be retained, however, and the symptom must not interfere substantially with thinking, social relations, or other behavior.

B. Frequency/Currency: The symptom or symptoms meeting criteria A must be present in the past month and occur at an average frequency of at least once per week in the past month.

C. Progression: The symptom or symptoms meeting criteria A must have begun or worsened in the past year.

D. Distress/Disability/Treatment Seeking: The characteristic symptoms are sufficiently distressing and/or disabling to the patient and/or others to lead to help-seeking.

E. Characteristic attenuated positive symptoms are not better explained by other DSM-V diagnoses.

F. Clinical criteria for any DSM-V frank psychotic disorder have never been met.