Children with CNV’s at higher risk for development of psychiatric disorders


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Mental health conversations have been fuelled with new impetus from the Government to start addressing the ever-increasing need and subsequent deficit the UK has for mental health support and treatment. Failings across the UK and councils not doing their utmost for some of the most vulnerable and debilitated individuals are now at the fore-front of what should have always been talked about. However, a lot seems to focus on those individuals which are already in the mental health system. We hear a lot about depression and anxiety, and rightly so, because of the prevalence of these. That doesn’t mean, however, that rarer conditions shouldn’t also get a ‘name-drop’. Let’s talk about schizophrenia, and let’s talk about those individuals who sometimes get missed when talking about mental health: children.

It is difficult to talk about disorders like schizophrenia, the symptoms of which are varied and wide-reaching. These can include ‘positive symptoms’ eluding to hallucinations, delusions and ‘racing thoughts’ or ‘negative symptoms’ such as apathy, mood fluctuation and absence of emotion valence. Understanding of these symptoms has been and remains to be limited despite tremendous bounds in work. In schizophrenia, early signs, or what we call ‘prodromal symptoms’ tend to be seen in early mid adolescence. A child experiencing these symptoms may or may not go on to develop schizophrenia – these symptoms are not deterministic, but in some instances can be early warning signs. Much work has been done to explore whether there are symptoms in childhood which could sound alarm-bells for individuals. These symptoms include changes in IQ and communication traits. These subtle or obvious changes could mean that children are at increased risk for schizophrenia.

The fact that these children, who do not have a diagnosis of schizophrenia but unknowingly could be at risk for its development, pertains to the reason why at the MRC Centre we work with children and adolescents with rare genetic conditions at an increased risk of developing schizophrenia. We want to understand the developmental and neurobiological pathways in individuals at high risk for developing schizophrenia to both help understanding and treatment in these particular children, but also shed light on the broader schizophrenia picture.

Both the ECHO and IMAGINE ID study in Cardiff work with a diversity of different copy number variant (CNV) genetic syndromes, but what is a copy number variant or CNV?  We work with children who have a rare genetic conditions. These genetic conditions are characterised by changes in DNA: a section of their DNA is missing or ‘deleted’ or there’s an extra bit or ‘duplicated’; like having a missing piece to a puzzle, or even having an extra bit. On average, an individual will have enough pieces of DNA to complete chromosomes, and to complete the puzzle. However some people have a bit too much or bit less. On certain chromosome, these changes can put children at increased risk for developing psychiatric and developmental disorders.

Children with a genetic syndrome called 22q11.2 deletion syndrome (22q11.2 DS) have a 20-30% increased risk for the development of schizophrenia. It is one of the highest known genetic risk factors for the development of schizophrenia. These individuals also have increased likelihood of ADHD, autism, anxiety disorders, oppositional defiant disorders, and epilepsy and sleep disturbances. This cocktail of different psychiatric problems is complemented by a myriad of physical problems including heart defects, breathing problems, abnormalities in their muscle and bone structure and cleft palate. This concoction of problems can mean that mental health problems can be exacerbated. For example, the continued and persistent sleep problems the majority of these individuals suffer from can interact with the mental health problems, making it harder to manage. If there are also physical problems, this could become an explosive mixture of problems.

Support for these families can be limited, with many health professionals not necessarily understanding the problems that they face; combine that with the wide-ranging conditions children with 22q11.2DS contend with, certain difficulties may get overlooked, with the focus being more on the obvious physical symptoms, rather than with the ‘less obvious’ mental health problems. Traditional mental health support systems can sometimes fail these families due to what some consider the added complication of the genetic syndrome. By working with these families, researching and understanding the difficulties that the mental health problems can impose upon both the child and the family itself, we can better work towards treatments and strategies to help not only these children with rare genetic syndromes, but children generally who are facing mental health problems worldwide.

Thanks to Hayley Moss for her contributions.