CCPR: Please tell us a little bit about yourself.
Dr. Ramsay: I’m a clinical psychologist at the University of Minnesota. I took a post-baccalaureate position in the psychiatry department at UC Davis, where I worked with Cam Carter’s lab studying the neural bases of aspects of cognitive disruption in people with psychotic disorders such as schizophrenia and schizoaffective disorder. Then I pursued a PhD in clinical psychology at the University of Minnesota, where I worked with Angus MacDonald, before going back to California to do my clinical internship at the San Francisco VA and UCSF. Now I’m back in Minneapolis and have a small lab of my own where we study aspects of neuroplasticity in people with serious mental illnesses. We’re interested in novel treatments that can target neural mechanisms to improve things like cognition, as well as overall function.

CCPR: What are the cognitive impacts of psychotic disorders in youth? What big-ticket items do we need to be thinking about?
Dr. Ramsay: Aside from the hallucinations and delusions commonly observed in psychosis, deficits in cognition also play a major role. There was a long period of time where researchers were trying to identify the specific deficits that people might show. Unfortunately, these deficits appear to be more generalized. People with psychosis experience deficits across most domains of cognition that we measure, such as working memory and attention, long-term memory, problem solving, processing speed, etc. The exact reasons why are not completely known, but a lot of us are trying to figure it out.

CCPR: How do these deficits affect function at school?
Dr. Ramsay: In young people especially, school is one of the first places where we notice these problems. In our community work, we train teachers and other staff members in schools to identify these early signs of the prodrome. One of the hallmark symptoms that we observe in the period ahead of a psychotic “break” or full psychosis (prodrome) is a decline in academic functioning such that students who seem to have been doing just fine, say in high school or early on in college, suddenly show a rapid decline (MacCabe JH et al, JAMA Psychiatry 2013;70(3):261–270). Some of this is related to the cognitive problems that I described, but it can also be related to some of the other symptoms that they could be experiencing such as delusional ideation, auditory hallucinations, or becoming more disorganized.

CCPR: Do you also see children and teens having problems with things like sleep, active daily living skills, or isolation from previous friendships/social situations?
Dr. Ramsay: Yes, these are all things that we consistently observe. The social one is pretty big. A lot of the patients that we see describe a period of time where they began to isolate, and then they often describe a period of time after they’ve maybe gotten treatment that they’re having trouble socializing the way they used to, whether that’s being able to track a conversation or to understand people’s intentions. We’ve got a lot of research suggesting people with psychosis have difficulty tracking and understanding facial emotions or intonations (Daros AR et al, Schizophr Res 2014;153(1-3):32–37). As you can imagine, it would be very difficult to interact socially if you were having trouble with attention and working memory and were also having trouble understanding the intonation of somebody’s voice. We don’t have pharmacological treatments that specifically target these things, so the challenge is to address them psychologically.

CCPR: How much do you rely on collateral information from family, teachers, or others? I have a collection of patients who think everything’s fine, but their families are really distressed.
Dr. Ramsay: Family support is paramount in this population. We have good evidence to suggest that people’s outcomes are better when they have strong, solid family support, and some of that comes down to sheer resources: having a safe place to be, having someone to help manage medications, having financial support. But also, patients’ families are our eyes on the ground, and we learn a lot from them.

CCPR: We need families to help—these patients do not have a sense that something is off.
Dr. Ramsay: Correct. We often observe this perplexing lack of insight early on in the illness: individuals who may have experienced a psychosis, even had a hospital stay, claim they don’t need support from their psychiatrists or psychologists or other therapists. We often have collateral information that things aren’t going as well as they think, though: They’re doing a little bit better, but they are continuing to suffer from some of those symptoms.

CCPR: So difficult. How does this play out?
Dr. Ramsay: I have an informal theory about insight in these situations. I call it my “two-hospitalization theory,” and it’s a pretty unfortunate one, because we don’t like to have patients hospitalized. But what I’ve noticed clinically is that a number of patients require a second hospitalization before they gain the insight and understanding that there is a pattern to their symptoms. In other words, what’s happening to them isn’t a mistake by the doctors; it isn’t because of the substances they were using; it isn’t something everybody else is making up. It’s really happening, and they begin to recognize that there really is a problem.

CCPR: Switching gears to treatment, we give people antipsychotic medications, and with luck their symptoms get a little better. But then patients complain that the pills are creating cognitive problems. Talk to us about cognitive side effects from the perspective of the professional who receives the patient on antipsychotic medications.
Dr. Ramsay: Yes, I deal with the fallout in these situations. A lot of these medications have a kind of anticholinergic cognitive profile where people describe a certain “fogginess” or sluggishness to their thinking. These are separate from the otherwise organic, cognitive deficits that people experience. We’re not helping people’s cognition. These problems are prominent early on when someone’s on an antipsychotic; but, in my experience, people begin to acclimate over time, and they experience less of that sort of dulling. If they get on a stable regimen with a good routine and can maintain consistency with that, then they can do really well.

CCPR: That’s somewhat encouraging.
Dr. Ramsay: But the point remains that people do have these side effects. We can try to manage them either with dosage modifications or other kinds of mitigation strategies.

CCPR: Can you give us some examples that have worked for you?
Dr. Ramsay: Taking medications at nighttime can help with daytime sedation. I’m also a big fan of long-acting injectable medications, as they seem to have this cognitive profile that might be present early on, but over the course of the month it may not fluctuate as much, which I think is probably a little more comfortable for people. With some of these second- and third-generation agents, we’re having a little better luck keeping people on them and causing fewer anticholinergic side effects.

CCPR: What is your take on rehabilitative programs to help remediate the cognitive impairments associated with psychosis?
Dr. Ramsay: A lot of my research is on cognitive training for psychosis. In the last 10 years or so, I’ve been examining whether computerized interventions might improve aspects of people’s cognition. What we know from the literature and our lab work is that, yes, we can rescue some of people’s cognitive abilities and create positive downstream effects on community or educational functioning and other things that are important in this population (Ramsay IS et al, Neuropsychopharmacology 2018;43(3):590–597).

CCPR: That’s hopeful too.
Dr. Ramsay: That said, we’re still trying to figure out how best to personalize these types of interventions, to tailor a training to fit the cognitive profile of an individual patient, to home in on the patient’s specific need. Our field is trying to figure out the optimal way to do that. But what we do know is that brains can change. A number of years ago, people thought that you couldn’t change the brain after it had matured, but we now know that isn’t true. The brain is changing constantly, well into adulthood. In adolescence and young adulthood, there is a critical period where we can capitalize on that plasticity. Our goal is to try to point the brain’s trajectory in an optimal direction. We’re still in the early phases of figuring out how to do that, but it’s a primary goal.

CCPR: How does this work with children and adolescents?
Dr. Ramsay: As far as tailoring these cognitive training interventions for younger populations—especially adolescents—a major goal is making them accessible and usable. That means making these challenging brain games fun, engaging, and portable. Ideally, individuals would engage in training daily, the same way one might try to exercise daily. With the technology to put these interventions on someone’s smartphone, we are trying to capitalize on the best way to do that. There is also emerging evidence that cognitive training can be neuroprotective for individuals at high risk for developing psychosis (Fisher M et al, Schizophr Bull 2015;41(1):250–258). Knowing this, it will be important to deploy these interventions in the right populations.

CCPR: Can you give us some idea of what the therapy looks like? What can we tell our patients about it so that they are better prepared for doing this therapy?
Dr. Ramsay: Most cognitive training programs are computerized and in many cases can even be accessed from a tablet or smartphone. These programs promote neural plasticity and learning by exercising aspects of basic sensory processing and attention. To do this, they use cognitive games—you have to click the right answer on visual tasks, calculations, mazes, concentrating on set shifting, etc—and they adaptively stay at a challenging level by either adding or subtracting stimuli or speeding up or slowing down the presentation of visual or auditory elements. They are challenging, but many people find them fun!

CCPR: What other measures are important to use, such as for educational planning or in guiding families or therapists on providing support?
Dr. Ramsay: In our clinics, we offer supportive employment and education, where a specialist works with patients in the community to identify how to re-integrate them into a job or help them get accommodations at school. The specialists also work with patients to improve their social life. It makes an incredible difference when you have someone working one on one to improve a patient’s functional well-being out in the community.

CCPR: This field is bearing fruit beyond schizophrenia. At UCSD, we borrowed heavily from your field to design executive function programs for organization skills in youth with autism spectrum disorder.
Dr. Ramsay: And beyond that, the brain is developing and changing well into adulthood, and we know that people as old as 80 can functionally change aspects of how their brain operates, which is a very hopeful story.

CCPR: So, you can train an old dog with new tricks. That’s truly encouraging. Finally, what practical tips do you have for child and adolescent psychiatrists that might help them to assess and advise their patients and families as a first step toward grappling with the cognitive problems associated with psychotic illness?
Dr. Ramsay: My most important advice would be to intervene early. As soon as someone has psychosis symptoms stably managed, it’s beneficial to start exercising cognition again (Loewy R et al, Schizophr Bull 2016;42(Suppl 1):S118–S126). In addition to computerized cognitive training, this can also look like starting to read again or even practicing paying attention for longer stretches. It may start with things like reading a newspaper or magazine before returning back to longer novels or textbooks. Another important point is assessment and tailoring an intervention to someone’s strengths and weaknesses. A quick cognitive assessment might reveal that one person has a weakness in attention while long-term memory is just fine. This could make a big difference in how a provider might tailor a cognitive training intervention (as in what types of exercises) and could also help a patient capitalize on current strengths.

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