Prevention has always been the cornerstone of initiatives to improve public health, based on the principle that it is generally better to recognize disease and intervene early rather than late. The prevention of psychosis in at-risk children is receiving the attention it deserves. Researchers in Denmark are leading the way. 

Profound implications for public health

The use of the large national health registries in Denmark has allowed investigators to compare the mental health of all children born to mothers or fathers diagnosed as having a serious mental illness (schizophrenia, bipolar disorder or major depression) with the offspring of unaffected parents.

For children born to mothers with schizophrenia, the relative risk of being diagnosed with a mental disorder before the age of 18 was 2.6; for the offspring of fathers with schizophrenia, it was 2.06; and, where both parents had a schizophrenia diagnosis, the risk was 4.6 times greater than in children in whom neither parent was affected. The most frequent childhood mental health problems were anxiety and ADHD.

Children who have a parent with schizophrenia have a higher risk not only of schizophrenia, but also of developing bipolar disorder or major depression. Around half of people with a mother or father with schizophrenia develop one or more mental illnesses, and a third develop a severe mental illness.

Intervention requires understanding

Of course, the risk is not attributable purely to genetic factors, Merete Nordentoft (Mental Health Center, Copenhagen, Denmark) said in her plenary lecture at EPA’s 2018 meeting in Nice. The environment and gene-environment interactions contribute; and this provides an opportunity for prevention. But it would help if we first understood more about how at-risk children develop.

Many at-risk children live in households with low levels of stimulation

Professor Nordentoft noted that we have had some evidence for a while, but many of the studies have been based on small convenience samples and lack the full range of measures and serial assessments that show how difficulties develop with time. The major Danish initiative is now seeking the address these deficiencies.

A large, longitudinal study

The High Risk and Resilience Study has recruited 522 families, 202 with children where one or both parents have schizophrenia, 120 in which one or both parents has bipolar disorder (BPD), and 200 controls. Assessment is intensive, lasting three days, and involves the children themselves, their biological parents, carers and schools.

An initial finding is that the home environment was judged inadequate – largely because of absence of stimulation – in 17% of cases where a parent had schizophrenia. This proportion was lower, at 5%, where a parent had BPD, and 2% in control families. Compared with controls, children from families with a parent with schizophrenia were more likely to have been the result of an unwanted pregnancy (11% vs 1%), more likely to have had a delayed start to schooling (17% vs 7%), and more likely to have experienced voices or visions.

At-risk children showed less awareness of others in a test of theory of mind

When assessed at seven years (the VIA 7 phase of the study), children at familial risk of schizophrenia showed less awareness of others in a test of theory of mind. They were more likely than children from control families to have language impairments and performed less well on assessments of IQ, fine motor skills, speed of visual processing, social skills and social functioning.

Can understanding lead to action?

The Danish team has now embarked on the follow-up phase where children – now aged 11 – repeat the assessments they had at the age of 7 and are also asked to have EEG and MRI. Of the 153 families approached to date, only four have declined to participate in the standard assessments and 80% of children have consented to MRI.

We hadn’t known so many children were living alone with mothers who have schizophrenia. Some children had had to adopt an almost parent-like role 

Professor Nordentoft and colleagues are well on the way to understanding how home environment contributes to risk and how markers of developing problems can be identified early. But their over-arching aim is to do something to help these at-risk children.

Funding has been obtained for the training of parents, psychoeducation in the children, and support for everyday activities or significant milestone events, such as having friends come over to the home for birthday parties. Arrangements are also being made to ensure fast-track access to care and treatment if problems develop.

We need to them develop a bag-load of resilience, Professor Nordentoft commented.