CCPR: How many children and teens have psychotic-like ­experiences (PLEs)?
Dr. Cadenhead: Research varies among longitudinal, ­cross-sectional, and general population studies. But roughly 9% of children and adolescents report a history of psychotic experiences. In children, ages 9 to 12, it’s around 17%. And in 13- to 18-year-olds, it’s about 7.5% (Kelleher I et al, Psychol Med 2012;42(9):1857–1863; Healy C et al, Psychol Med 2019;49(10):1589–1599). 

CCPR: What kinds of etiologies are involved? 
Dr. Cadenhead: The reasons for these PLEs include medication, substance use, schizophrenia, bipolar disorder (BD), depression, severe anxiety, trauma-associated symptoms, borderline personality disorder, or delirium (including delirium stemming from organic causes like infection or diabetes). And then there’s typical developmental fantasy, everyday tall tales, or just lack of good reality testing.

CCPR: How many youths with PLEs go on to have psychotic disorders?
Dr. Cadenhead: Teenagers and adolescents who report PLEs have about three times the odds of developing a mental disorder and four times the risk of developing a psychotic diagnosis. Diagnoses of substance use disorders, depression, or affective disorders are also common. About 40% of teenagers who use substances report having PLEs (Matheson SL et al, Psychol Med 2023;53(2):305–319). By the time these teens are 38 years old, about 93% of them have received a DSM diagnosis. So PLEs are a nonspecific marker of risk for mental illness (Healy C et al, Psychol Med 2019;49(10):1589–1599). 

CCPR: How do you differentiate psychosis from psychotic-like symptoms? 
Dr. Cadenhead: In our clinic, we look for insight. If an individual who has a PLE knows that what they are experiencing might not be real or might sound unusual, that distinguishes psychotic versus high risk. Large population studies are often done with questionnaires, and you don’t know how well the participant understands these symptoms, if they’re distressed by them, or if they have insight into them.

CCPR: Are specific etiologies of schizophrenia more common at certain ages? 
Dr. Cadenhead: The mean age of onset of schizophrenia is about 20 years old. About 18% have symptoms and 8% are diagnosed with schizophrenia before 18. In children under 12, the incidence of childhood-onset schizophrenia is about 0.05%, while early-onset schizophrenia (ages 13–17) has an incidence of 0.25% (Connor KD et al, Psychological Medicine 2012;42:1857–1863). Consider affective disorders, like BD or depression, or a severe anxiety disorder, like OCD with limited insight. PLEs can also occur with trauma, developmental disorders such as autism, and other genetic conditions. (Editor’s note: We recommend including trauma-informed care and responsive, relationship-based approaches in the care of patients with psychotic symptoms.)

CCPR: So how do you sort out the etiology in these cases?
Dr. Cadenhead: The history, physical exam, and screening lab tests can suggest other causes (Skikic M and Arriola JA, Child Adolesc Psychiatr Clin N Am 2020;29(1):15–28). We often don’t find a clear etiology. Instead, we need to wait six months beyond first-episode psychosis before calling it schizophrenia. Watch how the illness evolves, which may offer clues to the etiology.

CCPR: Isn’t schizophrenia a neurodevelopmental disorder?
Dr. Cadenhead: Schizophrenia is considered a neurodevelopmental condition with associated genetic and environmental factors, with brain changes in utero that manifest in late adolescence during key brain development periods. Sometimes you see clues in childhood, and the younger the onset of schizophrenia, the more likely the patient is to have profound cognitive, neurodevelopmental, and genetic abnormalities.

CCPR: Tell us more about how young patients experience PLEs.
Dr. Cadenhead: They are usually experiencing real distress. They might think they hear voices or sounds, think they see distorted images, or experience disorganization of their thinking. They can be confused, frightened, angry, or depressed. When they are fully psychotic, it’s real for them, and it doesn’t help to confront them and say, “That can’t be happening to you.” You must meet them where they are and find out what the experience is like for them. They might not want to leave the house or might worry their family will die if they don’t do a certain thing or believe something’s happened to them. Occasionally patients realize their experience sounds absurd, but that’s uncommon. They may become suicidal from the distress.

CCPR: How do you respond to their distress? 
Dr. Cadenhead: I talk with them about reducing the distress as opposed to making the symptoms go away. They might say, “I know this is happening” or “Something is controlling me,” and I’ll say, “I just want you to feel less distressed by this experience and help you to find other things to focus on.”

CCPR: Are there other aspects of PLEs we need to consider?
Dr. Cadenhead: Think about affective and nonaffective psychoses. This has a big impact on treatment. I try to distinguish between BD and schizophrenia and rule out things like medication or substance misuse causing it. Many people develop a psychotic episode after foreign travel. It may relate to disruption of circadian rhythm, and that’s more likely an affective psychosis. Rapid onset of symptoms often seems bipolar. If somebody has a reaction to an antidepressant, I wonder about rapid cycling, hypomania, or frank mania. Family history offers clues about whether the person is prone to bipolarity versus schizophrenia, in which case a mood stabilizer can help pretty quickly.

CCPR: How do we know when a patient has crossed from a PLE to a psychotic disorder?
Dr. Cadenhead: Use DSM criteria for schizophrenia, looking for hallucinations, delusions, negative symptoms, and disorganization of thought or behavior. Individuals will often spontaneously tell you that they have a problem (eg, worries that someone is stealing their thoughts), but you need to assess their insight. I’ll ask, “What do you think is going on?” If they firmly believe it is true, they are psychotic. For disorganizing symptoms, they must be severe enough to really interfere with their life because their behavior is so odd (eg, not being able to feed themselves, getting lost in the desert, etc). 

CCPR: Are some symptoms more predictive of future full-blown psychosis?
Dr. Cadenhead: We developed a risk calculator for psychosis as part of our research in the North American Prodrome Longitudinal Studies consortium via which the user can consider symptoms, demographic characteristics, and so on in relation to becoming psychotic. The more delusional symptoms—suspiciousness, paranoia, referential thoughts—are more predictive of psychotic disorders than hallucinatory phenomena, which have more possible etiologies. We also found two neurocognitive domains more predictive: poor verbal memory and reduced processing speed. A decline in social functioning seems related as well. Another study showed that traumatic stress, loss, and increased conscientiousness were associated with persistence of PLEs (Rammos A et al, Br J Psychiatry 2021;220(6):1–9).

CCPR: How do you use the risk calculator? 
Dr. Cadenhead: It’s not ready for general use among clinicians. We conduct a structured interview to identify prodromal symptoms. Yale University has training for the Structured Interview for Psychosis-Risk Syndromes (SIPS), and there are early psychosis centers across the country that have experience in this area (www.nationalepinet.org). This tool may be particularly useful in settings where there are a lot of young adults. For instance, I just spoke to our local naval hospital psychiatry department where they see first-episode psychosis all the time because patients are at the peak age of onset, and that setting could benefit from implementation of such a risk calculator. 

CCPR: How do you talk with patients and address their psychotic-like symptoms?
Dr. Cadenhead: For youth who meet the criteria for clinical high risk for psychosis per the SIPS, only 25% develop a full psychosis after two years, and we are studying how many more will develop a formal psychotic disorder after that. So, we say, “You seem to be at risk for potential mental health problems, and we want to prevent that.” Then, depending on the situation, we could say, “You’ve been through a lot of stress recently; this may be contributing to some of your symptoms.” Then we work with the family and their environment to decrease stress—because for young people, that’s often the most important approach. They may need an Individualized Educational Plan at school or to take a semester off college, depending on the functional disability that they have because of their symptoms.

CCPR: What does treatment look like for youths with PLEs? 
Dr. Cadenhead: We have an early psychosis program that treats both people considered clinical high risk and people in their first episode of psychosis. We want everybody, whether they’ve had a psychotic break or not, to see a therapist. We also have group therapies, one wellness oriented and another one featuring dialectical behavior therapy and focused on mood. We sometimes use the Department of Rehabilitation, and we’ve worked with supported employment organizations. We also plan to add a peer support program. We focus on wellness: not using drugs, healthy diet, exercise, getting up early, getting light. These interventions reduce stress, improve mood, and improve circadian rhythm, all of which reduce inflammatory responses related to stress. The evolving research on the care of patients with PLEs begs for a continuing conversation between researchers and clinicians (Uhlhaas PJ et al, Mol Psychiatry 2023;28(8):3171–3181). 

CCPR: How do social determinants (culture, socioeconomic status, or environmental factors) impact care of these patients? 
Dr. Cadenhead: There are many environmental risk factors and sociocultural factors that can influence the development of psychosis or are just associated with psychosis, including living in poverty, lack of green space, and poor nutrition. In the San Diego area, there are immigrant families that have high expectations about their teenage children academically or in terms of family support, which we know is so important (Correll CU et al, Eur Neuropsychopharmacol 2024;82:57–71). So, there’s often more pressure than I’d like to see on the child to go back to school or work. And some cultures don’t see psychiatrists but are forced to due to legal issues or after a hospitalization. 

CCPR: Are there other social determinants to consider?
Dr. Cadenhead: Sure. Are their parents working with heavy metals? Is there lead in the pipes? Are they eating raw meat? Are they around cats that might contribute to toxoplasmosis or other parasitic illness? Ask about religious beliefs regarding the patient’s symptoms; try to determine what about the symptoms is extreme or out of the norm for the family. I have a recent publication on protective factors that found that people from Hispanic backgrounds are less likely to become psychotic, even if they have high risk on the calculator. Another group found that if an immigrant lives in a place where there are many families from the same country, the chance that their PLE will become a psychosis is much lower. Maybe with a large community, there’s more support (Cadenhead KS et al, Schizophr Bull 2024; Epub ahead of print).

CCPR: So interesting. Do you have any summarizing or concluding thoughts? 
Dr. Cadenhead: Look at this group as distressed and with a broad differential diagnosis. People with PLEs are at high risk for mental health problems in general. Schizophrenia is one of those, but they are comorbid for many mental health problems. Address those things that are specifically treatable and unique to that individual. By doing that, you can reduce the patient’s distress and reduce their odds of having to be hospitalized or developing a more serious mental health problem that can cause lifelong disability. 

CCPR: Thank you for your time, Dr. Cadenhead.