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Scientists identify links between psychiatric disorders and events during the foetal stage

The causes of mental disorders may stem from the earliest stages of pregnancy, during foetal neurodevelopment. This is shown in a study published in Nature Neuroscience, conducted by scientists from the Lundbeck Foundation Initiative for Integrative Psychiatric Research.

Particular genetic variants in human DNA, which are important for the development of the brain early in the life of the foetus, are highly prevalent in people with psychiatric disorders. This was discovered by scientists from the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH). They studied a total of eight million genetic variants and found that a number of these variants are highly prevalent in people who suffer from one or more of these psychiatric disorders: schizophrenia, depression, bipolar disorder, autism and ADHD.

Professor Thomas Werge, from the University of Copenhagen and one of the scientists behind iPSYCH into which the Lundbeck Foundation has injected a total of DKK 361 million, explains:

‘If we look at these genetic variants more closely, we can see that they’re linked to genes which are active when synapses are developing in the brain of a foetus – in other words, when the ‘wires’ that connect neurons are formed. And this means that the causes of mental illness may actually be traced back to a time in pregnancy when the foetus’s brain was under development.’

Thomas Werge headed the study, which was recently published in the scientific journal Nature Neuroscience. The Danish contingent of the research team included scientists from the University of Copenhagen, Aarhus University, Statens Serum Institut (SSI) and the Technical University of Denmark. Researchers from Australia, Switzerland and the USA also participated.

Extensive battery of blood tests
There has long been an assumption among scientists who study psychiatric disorders that psychiatric diagnoses share particular genetic variants. This assumption is also based on the fact that a range of psychiatric disorders are often seen together – both in families and in individuals.

Thomas Werge explains that the assumption has been tested in a range of studies but never involving an entire population:

‘And that’s exactly what we’ve done; we’ve looked at an entire population – the Danish population. This gives us the highest possible degree of statistical certainty, because we can exclude a wide range of coincidences, for instance to do with selection of study materials. At the same time, we get an extremely detailed picture of all of the mental disorders people can suffer from.’

The study behind the article in Nature Neuroscience is based on blood samples taken, with the consent of the parents, from most newborns in Denmark. These are so-called heel prick tests, also known as PKU tests, to which scientists have access – although always in anonymised form.

The PKU archive is the only one of its kind worldwide, and by examining the DNA profiles of all tests taken between 1980 and 2005, Thomas Werge and his colleagues were able to conduct an exceptional study.

The samples are linked to the Danish health system’s civil registration (CPR) numbers. This means that, in addition to the entire DNA of the person in question, the journal behind the individual PKU test contains in anonymised form much of the health data stored about the person in the public health system. This includes information about psychiatric diagnoses.

‘When we looked in 2012 at the journals linked to all of the PKU tests taken between 1980 and 2005 – a total of around 1.5 million – we were able to see that 46,000 people from this group had developed one or more of the major psychiatric disorders. And we compared their DNA with the DNA of a sufficiently large number of people in the register who had no psychiatric diagnosis,’ Professor Thomas Werge explains.

A question of vulnerability
But what do these discoveries mean? Will the genetic variants that proved in the study to be highly prevalent in people who have been diagnosed with one of the five major psychiatric disorders definitely trigger the disease?

‘No, it’s not that simple,’ says Professor Thomas Werge: ‘It would be more correct to say that these genetic variants make you more vulnerable to developing a psychiatric disorder. And this means that a combination of vulnerability of this kind and environmental impact – for instance, stress, infections or perhaps factors such as vitamin deficiency – may well be the straw that breaks the camel’s back.’

In addition, the first author of the scientific article, iPSYCH’s research director Andrew Schork, points out ‘that our study shows that the seeds of a mental illness that appears late in life may be sown much earlier’.

Thomas Werge believes that this knowledge about links between psychological vulnerability and genetics produced by the new study could be used in preventive contexts:

‘This knowledge may help us identify positive environmental influences to improve our advice to pregnant women on what they should avoid to protect or prevent psychological vulnerability in the foetus.’

For further details please contact:

Thomas Werge, professor at the University of Copenhagen and affiliated with iPSYCH, tel. +45 2218 6734

Henrik Larsen, science journalist at the Lundbeck Foundation, tel. +45 2118 6377 or hl@lundbeckfonden.com

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