Mind Meets Body in New Lupus Research: Q&A With Andrea Knight, Rheumatology Physician

When children have lupus, they often deal with more than just the physical burden of the autoimmune condition. Along with the swollen joints, skin rashes, ulcers, kidney disease and chest pain common to lupus, many of our pediatric patients also carry with them depression, anxiety, memory problems, and brain fog – all of which can adversely affect their school and social lives. As the recipient of a Novel Research Grant from the Lupus Research Alliance, Andrea Knight, MD, a physician in the division of Rheumatology, is working to better understand why children with systemic lupus erythematosus (SLE) experience mental health problems. Novel Research Grants aim to support investigators in early stage research projects that involve “creative and innovative approaches” to major issues in lupus, according to the research alliance’s website.

Dr. Knight’s research will give new depth to current clinical knowledge of lupus and help physicians treat neuropsychiatric conditions earlier and more effectively. Her previous research has found that children with SLE have high rates of depression, anxiety, and suicidal thoughts, but most of these children have not had mental health evaluation or treatment.

We spoke with Dr. Knight on how we can best identify and address mental health concerns in children with lupus and the next steps for improving their outcomes.

What do we know about the link between lupus and mental health so far?

For children and adolescents with lupus, we know that they are at higher risk for depression and anxiety than their healthy peers, but they have a similar risk to kids with other chronic conditions such as Type 1 diabetes or juvenile diabetes. So, within the context of lupus, there is an open question about whether the depression and anxiety risk is a comorbidity related to having a chronic disease, or whether it’s actually related to the inflammation that affects the central nervous system in the disease. That is the clinical question that we’re interested in.

How many children with SLE experience neuropsychiatric conditions?

The number of children with lupus who experience depression and anxiety really is quite high. It’s basically up to a third of those with the condition, and some studies will indicate even higher – 50 or 60 percent. Again, we’re not really sure whether that depression and anxiety is a comorbidity related to having a chronic disease, or if it is related to the brain inflammation.

What do we currently know about biological mechanisms like brain inflammation that might underlie these neuropsychiatric symptoms?

I think that with brain inflammation in lupus, there are a number of different mechanisms that have been proposed. Some people think that it may be due to antibody-related inflammation that might be localized, meaning that the antibody is acting on brain tissue to cause inflammation.

Then there are other mechanisms that are proposed that involve indirect inflammation: Perhaps the inflammation is due to cytokine release or other inflammatory mediators, either originating in the brain or elsewhere in the body, getting across the blood-brain barrier into the brain. Another potential mechanism involves vascular changes and alterations of blood flow in the brain. So, we’re not sure whether those mechanisms act individually, together, separately, or whether there’s another mechanism that we’re not really aware of.

Can you describe how you’re moving forward with your Novel Research Grant?

Well, building on a few studies that have been done by colleagues at other institutions, we’ve realized that using advanced brain MRI neuroimaging techniques can go past what we do clinically with conventional MRI to identify changes that are happening in the brain. So, what we’re looking at in children with SLE are structural changes in the different regions of the brain, as well as differences in function of brain networks, and also changes in brain development that happen over time, in comparison to healthy peers. We are looking at how these changes on the advanced imaging correlate to the emotional or psychological dysfunction that we would see in those who have depression and anxiety, and if they differ for children with SLE.

And then, bringing in the inflammatory mechanisms, we are looking at proteins in the blood that are implicated in brain inflammation and their correlation to the imaging to psychological manifestations. We hope to get some insight into a possible inflammatory signature that might help us to determine which kids are having depression and anxiety as part of the inflammation, versus as a comorbidity related to the burden of chronic disease.

What are the wider implications after your research is done?

I think there’s a couple of things. One, increasing our understanding of the mechanism, since we really still don’t quite understand the mechanisms of brain inflammation and brain effects of lupus in these children, could have broader application to other brain inflammatory disease, as well as the contribution of inflammation to primary psychiatric disorders. Two, it would be a goal to take that understanding and apply it to clinical management to try to inform our clinical decision-making, so that we can really offer more personalized and targeted therapies addressing emotional disturbances and neurocognitive function for these kids.

Do you have any guidance for physicians treating children with lupus?

I think that in our pediatric lupus population it is very important for all of the clinicians involved in lupus care, from rheumatologists to the different specialists, including a child’s primary care doctor, to be aware that emotional distress and psychological dysfunction like depression and anxiety are relatively common in likely a third of these patients. Early intervention is really key. And then as we – through ongoing research – become more fine-tuned with our understanding of the mechanisms, our diagnostic tools and treatment tools will hopefully be able to further improve the outcomes for these kids. One of the things that can help with this is routine screening of these children and adolescents for things like depression and anxiety and then trying to get them services earlier rather than later.

When do you hope to get findings out?

The recruitment for this study is scheduled for two years, so I am aiming to have some preliminary data within that time frame and get the findings out as soon as possible. Just from a logistical standpoint with the MRI study, this is relatively new area for me, so I don’t have a feel quite for how our recruitment will go, but in a couple of years, we’ll have something cooking!

Is there anything else you want to add?

It’s exciting to have interest from the Lupus Research Alliance in this kind of work, and I think it’s an area that’s really ripe for research, so hopefully this funding will be a building block to future projects and also collaborative projects with other researchers who are interested in this topic.