Genetic anomalies in children and adolescents with PANS
7 september 2022
PANS stands for Pediatric Acute-onset Neuropsychiatric Syndrome and describes a group of children where research shows that an underlying disease of the immune system may contribute to the development of symptoms. An international research collaboration is studying a patient group of 400 children and adolescents with PANS.
The syndrome is still relatively unknown, lacks established markers and does not yet have an established diagnosis in Swedish healthcare. In these cases, patients suddenly develop unusual and severe symptoms, with their personality, behaviour and abilities changing drastically. There may be treatments and cures for these children if the underlying mechanisms are understood, but it often takes time and can be difficult for many patients to get the correct diagnosis.
Janet Cunningham, a specialist physician and docent in clinical immuno-psychiatry at Uppsala University, has spent many years examining patients whose problems are suspected to be due to immunological mechanisms. In consultation with experts in neurology, rheumatology, neuroradiology and clinical immunology, she has developed a special clinic for immuno-psychiatry. The clinic investigates and treats patients with established or suspected autoimmune diseases of the nervous system, which cause psychological symptoms.
Sudden behavioural changes
She is currently involved in an international and multidisciplinary research collaboration studying a patient group of 400 children and adolescents with PANS from Europe and the US. The initial study shows genetic anomalies that are extremely rare and very likely to affect both the innate immune system and communications between nerve cells in the brain.
“Patients with PANS, who previously functioned well socially in groups and performed well at school, suddenly develop severe obsessive-compulsive disorders, stop talking, and have difficulties with aggression, sleep, eating disorders and schoolwork,” says Janet Cunningham. “They also experience emotional dysregulation with anxiety, depression and psychotic signs. It comes on suddenly and many parents have reported a history of infections.
“The biological links are difficult to capture because the variation in biological mechanisms is so great. But in this study, we have made a breakthrough and framed key processes in the innate immune system. We have also revealed previously known mutations in ‘neuronal’ genes that may affect immune system function in the PANS group.”
Family members severely affected
Clinical immunopsychiatry is a new field of research with great potential to find new treatments in healthcare. In every psychiatric diagnosis group, there is a proportion of patients with immunological abnormalities of different types.
For example, patients with autoimmunity are more likely to have obsessive-compulsive disorder (OCD), autism and psychotic disorders in the immediate family. While a low-grade inflammation, which may be associated with the risk of diabetes and obesity, is more common in the patient group with affective symptoms such as depression and anxiety. But there are also other anomalies, including difficulties in coping with different types of infections, or limitations in the body's ability to repair itself after an injury.
“Empirically, we know that some patients in this group can have astonishing responses to immunotherapies, so this is something we will continue to investigate before we can introduce it clinically. Our focus now is on being able to identify patients with immunological dysfunction with objective tests,” says Cunningham.
“In my view, children, as well as adults with acute psychiatric conditions, are not getting satisfactory symptom relief from the available standard treatments. They are also over-represented among patients with severe side effects. These conditions cause great suffering to individuals and are also hard on families. Unfortunately, particularly in the absence of a diagnosis, patients are often left out of the usual services available, such as support at home and parental relief. Many have had to give up their jobs because they need to care for their children full-time. They are left out of all the systems for getting social help.”
“We have recently developed preliminary guidelines for the investigation of autoimmune OCD and psychosis in patients where symptoms are suspected to be secondary to autoimmunity. We are continuously working to improve these guidelines and to pay attention to other differential diagnoses, such as underlying metabolic disorders and immunological deficiencies. But to be fully successful, we need to establish an improved chain of healthcare with a clearer division of responsibilities across medical specialities. We also need a budget that matches the costs of investigation and treatment and increased research resources for these severely affected patients.”
Optimal treatment for each patient's condition
"This study shows the potential for a way forward in working towards a more integrated approach to mind and body. Here we can take advantage of precision medicine, which is about integrating new biological variables all the way down to the patient level, to test new treatment strategies that target specific mechanisms for that particular patient. The different genetic anomalies we have identified in the study create new groupings, which in turn require more personalised treatment.
“But precision medicine is fairly new in psychiatry. Historically, the focus has been on psychological treatments where we have seen tremendous progress and we have a set of medications that work well for symptom management. But now I think psychiatry can learn from somatics, which has come further in precision medicine. My hope for the future is that we can build a system of care with multidisciplinary teams based on a more integrated approach and work between the specialities of psychiatry and somatics,” concludes Janet Cunningham.