Early Risk of Psychosis and Prodromal SyndromesCCPR: Dr. Bearden, please tell us about the prodromal phase and how it is identified.

Dr. Bearden: When a young person meets a set of criteria that appears to indicate he or she may develop a psychotic disorder, we call it a “putative prodromal syndrome.” It is putative because we don’t know exactly where people are headed, or if psychosis is the ultimate outcome. There are basically three distinct prodromal syndrome criteria. These include attenuated or subthreshold psychotic-like positive symptoms, a recent period of brief full-blown psychotic symptoms, and genetic risk.

CCPR: Please explain each of those briefly.

Dr. Bearden: First, attenuated or subthreshold psychotic-like positive symptoms are things like unusual thought content, suspiciousness, grandiosity, perceptual abnormalities, and disorganized communication. If someone comes in with one or more of those symptoms that has either started or worsened in the past year, then they would meet criteria for what is called an “attenuated psychosis” or “attenuated psychotic symptom prodromal state.”

CCPR: And how about the criterion related to brief periods of psychotic symptoms?

Dr. Bearden: This is known as a “brief intermittent prodromal syndrome.” These are people who have very recent onset, fully psychotic symptoms that are very brief in duration—sometimes only minutes long—that do not yet meet criteria for a full-blown psychotic disorder.

CCPR: And the third criterion?

Dr. Bearden: The third criterion by which people could be considered prodromal is what we call a “genetic risk and deterioration” category. A genetic risk is defined by either having a first-degree relative with a psychotic disorder or if the subject themselves meets criteria for schizotypal personality disorder. Either of these, in combination with a recent decline in functioning, puts someone in the category of a putative prodromal syndrome.

CCPR: What does the research show happens to young people who meet these criteria in the long run?

Dr. Bearden: Well, for our multisite longitudinal study in the United States, we include people between the ages of 12 and 35, because that is the greatest risk period for the development of psychosis. Most of the people we follow are between 15 and 22. So we follow them for a period of two years, and over that two-year period about 25 to 30 percent of those meeting these prodromal criteria will develop a full-blown psychotic disorder (Cannon TD et al, Arch Gen Psychiatry 2008;65(l):28-37).

CCPR: How do you differentiate between a psychotic episode or first psychosis that could be related to something like schizophrenia versus psychosis that is part of either a depressive or bipolar episode?

Dr. Bearden: In the prodromal stage, we define psychosis very broadly, because we really aren’t able to say with any certainty at this point that these symptoms are headed toward bipolar psychosis or schizophrenia. That is something that many investigators are working on. When we look at diagnostic outcomes among those individuals who do develop a full-blown psychotic disorder, about 75 percent of those are schizophrenia spectrum diagnoses, but many of them over a two-year period are psychosis not otherwise specified (Fusar-Poli P et al, Arch Gen Psychiatry 2012;69(3):220-229). So the full clinical picture hasn’t really crystallized at that point.

CCPR: What other risk factors are there?

Dr. Bearden: One of the biggest risk factors in the general population is having a first-degree relative with a psychotic disorder. A recent decline in both role functioning and social functioning can be red flags as well. We don’t see a ton of disorganized communication in the really early stages, but if you do see it, it is probably a bad sign. This would be characterized by any kind of loose association or unusual use of language—a story that is really hard to follow or tangential, for example. Thought-related items, the so-called “positive symptoms,” are the most predictive of conversion to a psychotic disorder. These would include unusual thought content and suspiciousness. Additionally, certain genetic conditions like a 22q11.2 deletion [the deletion of a small section of chromosome 22] can dramatically increase psychosis risk.

CCPR: What do we know about the role of cannabis in a first episode? This has been a recently controversial topic.

Dr. Bearden: This is an active area of investigation. In the first study from our consortium to investigate multiple risk factors, we found a relationship between cannabis use and first episode of psychosis (Cannon et al, op.cit). But in our most recent sample, we didn’t find that increased rates of cannabis use at baseline was predictive of a subsequent conversion to a full-blown psychotic disorder among people who are already defined as clinically at-risk according to these prodromal criteria (work in progress). That being said, in population-based studies they do find that cannabis use increases your odds of developing psychosis by about 1.5 (van Winkel R & Kuepper R, Annu Rev Clin Psychol 2014;10:767-791).

CCPR: So the picture is murky.

Dr. Bearden: I am not going to comment on people in the general population, but for people that are experiencing prodromal symptoms, I can say with a pretty good level of confidence that smoking pot is not helping the symptoms, even though some people who are experiencing these distressing symptoms really think that it is. The research is difficult because in these studies that are focused on clinical high-risk population, if people have a certain level of drug use then we won’t include them in our sample because we can’t conclusively say that the drugs aren’t causing the symptoms. I would say about half of the putatively prodromal patients in our study smoke pot at least once a week. But for people that are using much more frequently than that, we can’t include them in the study because it is just too hard to distinguish what is causing the symptoms. So I think that is part of why we may not be finding a relationship, whereas in epidemiologic studies they do.

CCPR: How do most people come to your specialty clinic?

Dr. Bearden: The majority of referrals come from other mental health providers, including inpatient psychiatry units, primary care physicians, and schools. We also get a lot of referrals from programs focusing on autism and OCD because they will often have kids who sort of look like OCD or autism, but there seems to be something else going on.

CCPR: Please tell us a little more about how kids come to you by way of school referral?

Dr. Bearden: Not always, but usually, these tend to be less severe at that point. These are kids who are typically having a decline in school or having some odd behavior. School is probably one of the biggest sources of stressors for these children, so in September we get a ton of calls. Just getting a kid into a better school environment, even with no additional intervention, can make a really big difference.


 

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This article was published in print Summer 2014 in Volume:Issue 5:4.