Risk of mental disorders appears higher in youth who had COVID-19

[00:00:00] Host Amber Smith: Upstate Medical University in Syracuse, New York invites you to be "The Informed Patient" with the podcast that features experts from Central New York's only academic medical center. I'm your host, Amber Smith. The COVID years were rough for so many people, including children. A study from researchers at Upstate looks closely at the impact COVID had on mental disorders with some interesting findings. Here to tell us about them is Dr. Yanli Zhang-James. She's an associate professor of psychiatry and behavioral sciences at Upstate. Welcome back to "The Informed Patient," Dr. Zhang-James.

[00:00:38] Yanli Zhang-James, MD: Thank you for having me, Amber. I'm really excited to share with you our research on the impact of COVID-19 and youth mental health.

[00:00:48] Host Amber Smith: Well, what made you and your team want to look at the impact COVID had on children and adolescents in terms of mental disorders?

[00:00:56] Yanli Zhang-James, MD: I'm a neuroscientist by training, and my research has been primarily focused on ADHD, (attention deficit hyperactivity disorder.) So I've long been interested in mental health issues in children and adolescents. But I've also considered myself a health informatician and an avid AI (automated intelligence) machine learning practitioner. So this line of work has intersected with COVID-19 studies at the start of the pandemic.

In 2020 I was working with colleagues in our computational psychiatry and public health divisions to develop AI machine learning models to predict COVID cases in our county. While I was working on the COVID forecast, I started to explore more about the interactions, relationship between ADHD and COVID and came across many interesting readings. For example, the historical studies on the 1918 flu pandemic some have reported that increased emergence of minimal brain dysfunction in children in the decades after that pandemic. That was the name for ADHD.

So we started working on the interaction of ADHD and COVID with the hypothesis of it's a bidirectional relationship, that kids who have ADHD may more likely put themselves at risk of contracting COVID and also the other direction of the relationship, that having COVID potentially can lead to more ADHD diagnoses.

So we started to leverage a large medical record database that we had access to in examining these relationships. By the time we published the first part of the paper that ADHD is a risk factor for COVID, it became clear that the impact of COVID extended far beyond ADHD. There were many reports on more diagnoses of anxiety, depression, issues with brain fog, cognitive problems and sleep problems. But the problem with the, at the time, the (scientific) literature heavily focused on the pandemic, not specifically on the COVID infection itself. And most of the literature was on adults, so there was less learned about the impact on children. And that's why we started the second study.

[00:03:19] Host Amber Smith: Now were you and your colleagues at Upstate seeing more diagnoses of mental disorders in youth?

[00:03:25] Yanli Zhang-James, MD: Yes, we did. Our research on this large medical record analysis found four to six times of increase of risk acquiring new diagnosis of any mental disorders in youth. And in a separate study we also look at Upstate ER (emergency room) visits that we saw during early COVID. Despite there was significant drop of ER visits, but the number of psychiatric visits to ER remained stable, and that resulted in the increase of proportion of psychiatric ER visits in children.

[00:04:02] Host Amber Smith: Now, when we talk about COVID infection, are we talking about just having been infected and become sick with COVID, or are we talking about the "long COVID" that we've heard about where you have some symptoms that linger for months or years?

[00:04:18] Yanli Zhang-James, MD: Right. So the COVID we examined in this particular study was defined as acute infections. But what we measured is the long lasting impact, in terms of new diagnosis of mental disorders in the two years following that initial infection. So you could consider that's part of the long COVID.

[00:04:41] Host Amber Smith: I see.

Well, let's talk about how you structured your study. How many children were involved, and up to what age did you look at?

[00:04:49] Yanli Zhang-James, MD: Our study is considered a retrospective cohort study. So that means we are comparing two cohorts. We identified a cohort of kids who had COVID infections, either by positive laboratory tests, or had an ICD (International Classification of Diseases) diagnostic codes for COVID in their medical records.

Then we find another cohort of kids who never had the infections during the same study period, but they had encounters to the health care system, so they had visited doctor for other reasons. Now we compare them during the two year follow up to see which group had more diagnoses of mental health problems.

[00:05:29] Host Amber Smith: The database you're working with, is it national, or is it geographic? Are you looking at certain areas of the country, or the entire country?

[00:05:38] Yanli Zhang-James, MD: We are looking at the entire database from the TriNetX (Research Network,) which is representing about over a hundred million patients, total patients. There were, a small proportion were from outside of the U.S., but vast majority, like 99% of data, were from U.S. We do not have the geographic location distinctions.

[00:06:02] Host Amber Smith: You are listening to Upstate's "The Informed Patient" podcast. I'm your host, Amber Smith. I'm talking with Dr. Yanli Zhang-James, an associate professor of psychiatry and behavioral sciences at Upstate.

So let's talk about your results. Were kids who had COVID more likely to acquire a new psychiatric diagnosis?

[00:06:24] Yanli Zhang-James, MD: Yes. That's exactly what we saw.

We found a remarkable increase of increased risk of acquiring new diagnosis of mental disorders in both children and adolescents. For example, for children, the increase of risk was from 2.6% to 15%. And for the adolescents, compared to the non-infected adolescents, the risk increased from 5% to 19%.

[00:06:54] Host Amber Smith: Why do you think it was higher for the younger children?

[00:06:58] Yanli Zhang-James, MD: That's an interesting question. Certainly the children's brains are less mature. They're more vulnerable for potentially dysregulated immune functions, those insult into their developing brains. I think other explanation could also potentially involve, for example, less coping skills to deal with social isolation, the stress in the family. I think it's a combination of the unique risk period and uh, environmental factors.

[00:07:40] Host Amber Smith: Did you see variations based on gender?

[00:07:43] Yanli Zhang-James, MD: We did. We found significant gender based differences in the mental health outcomes. Primarily we saw highest risk in female adolescents, followed by male children, and then male adolescents, then female children.

So it seems like the female, girls had a higher risk during adolescence, but the boys had a higher risk in childhood. While this may suggest that boys are more vulnerable in childhood, girls are more vulnerable in adolescence, but this could potentially just reflect on the diagnostic practice in these two age period.

We know that neurodevelopmental disorders like ADHD and conduct disorder were more likely to be diagnosed in childhood, and in boys, while mood disorder and anxiety are more likely to be diagnosed in girls during adolescence. I think, certainly more research needs to be done to better understand this biological impact on the gender disparity.

[00:08:53] Host Amber Smith: Did you look at differences between how severe of an infection the person had?

[00:09:01] Yanli Zhang-James, MD: We did. We observed an interesting dose response relationship where more severe COVID cases were linked to higher risk of mental disorder diagnosis. So for example, we compared between inpatient and outpatient COVID cases. We also compared those who simply tested positive compared to those who also had confirmed diagnostic codes. So these are potentially different severities.

[00:09:34] Host Amber Smith: Now, your study didn't get into the reasons why the risk for psychiatric diagnoses increase. But do you have theories about that, why this goes up and if it's biologic? Is it caused by the virus, or is it caused by, a lot of us were in lockdown for quite a while, and there was a huge impact on our lives. Did that play into this more?

[00:09:58] Yanli Zhang-James, MD: You are absolutely right. It's a combination of both. The leading hypothesis, I think, is about centered around neuroinflammation. When you have a severe infection certainly there's a host of immune responses in our body, and during the infections are for example, the barrier between brain and blood could potentially be weakened and more permeable. So these molecules can potentially impact brain function. But besides these biological reasons, psychosocial stress certainly plays a significant role that could potentially change our brain functions.

[00:10:40] Host Amber Smith: And you said historically there's evidence, other serious respiratory infections this has been seen in. You mentioned the 1918 flu pandemic.

[00:10:49] Yanli Zhang-James, MD: Yeah, that's very interesting to me. Initially, the increase of minimal brain dysfunction, for example, in the decades following that pandemic. And now we know that's a terminology for ADHD. In 1950s and sixties, some of the leading expert did suggest that infections such as this could lead to more neurodevelopmental disorders in years and decades following a pandemic such as this.

Dr. James Swanson -- he's a leading ADHD expert -- and Dr. Nora Volkow, the director of National Institute on Drug Abuse, wrote a letter and the title was "Lessons from 1918 Flu Pandemic, A Novel Ideological Subtype of ADHD," highlighting that the hypothesis that we may be seeing more ADHD diagnosed in coming years and decades.

But our research clearly showed that we're going to see a lot more diagnosis of a wide range of mental disorders.

[00:11:55] Host Amber Smith: What is the takeaway message from your study, in terms of what do parents of children who had COVID need to be aware of?

[00:12:03] Yanli Zhang-James, MD: Our study is a clinical epidemiology study. It looks at the association or correlation. It's not a causation. So we're not saying that, for sure, cOVID is causing mental disorders, but the association is strong and clear, whether it's through neuroinflammation, immune dysregulation or psychosocial effect of having the infection itself, or the compounding effect of pandemic isolation, the psychosocial stress associated with all that.

COVID-19, it definitely has a significant and long lasting impact on the youth mental health, and early screening and monitoring for these mental health concerns in youth, particularly among those who are already at risk, is important. I think interventions and improved support for at-risk youth should be a public health priority.

So communicating with the public about these concerns and is certainly a main interest of me and our colleagues. For parents, I think this research highlighted that we -- myself included; I'm a parent -- we should be fully aware that there could be mental health challenges emerging after an infection. It could be months or years later. We need to watch out for symptoms, a wide range of symptoms. For example: persistent sadness, excessive worry, social withdrawal, irritability, aggression, problems at school, problems with sleep. If there's something off, reach out to pediatrician, to mental health professionals to seek help.

There should be also implications for pediatrician. Incorporating mental health screening is important for even routine pediatric visits, particularly for those kids who had COVID previously. And I think pediatrician should play a critical role in educating public, their patients and their family, their parents about research findings such as ours. I think informing their patients and their family about the potential long-term impact is important, and encouraging them to seek help if needed.

[00:14:37] Host Amber Smith: Thank you so much for making time for this interview, Dr. Zhang-James.

[00:14:41] Yanli Zhang-James, MD: Thank you.

[00:14:42] Host Amber Smith: My guest has been Dr. Yanli Zhang-James. She's an associate professor of psychiatry and behavioral sciences at Upstate. "The Informed Patient" is a podcast covering health, science and medicine, brought to you by Upstate Medical University in Syracuse, New York, and produced by Jim Howe with sound engineering by Bill Broeckel and graphic design by Dan Cameron. Find our archive of previous episodes at upstate.edu/informed. If you enjoyed this episode, please invite a friend to listen. You can also rate and review "The Informed Patient" podcast on Spotify, Apple podcasts, YouTube, or wherever you tune in. This is your host, Amber Smith, thanking you for listening.