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Five 'mental disorders' may have genetic links

Sky News reports that, “five of the most common psychiatric disorders are genetically linked.”

This news is based on a landmark study that examined the genetic sequences of more than 50,000 people. Some of these people had one of five common long-term conditions the researchers called ‘psychiatric disorders.’ These were:

This useful and well-conducted study provides an invaluable insight into the possible genetic factors linked to these common mental health disorders.

Researchers found variations in four genetic regions were associated with these disorders when they looked at the DNA of people who had been diagnosed with one of the mental or behavioural conditions.

Some of these genetic variations affect how calcium moves through the brain. These findings have given rise to speculation about the possibility of new treatments being developed for these conditions.

However, reports that genetic testing could be used to predict or diagnose mental illnesses are probably wide of the mark. The researchers have stated that the effects of the genetic variations are small, and that on their own the variations would not be useful for predicting or diagnosing these conditions.

It is also simplistic to regard mental health conditions or behavioural problems as being purely genetic. There is a wide range of rigorous evidence that shows that environmental factors are also involved.

Where did the story come from?

The study was carried out by researchers from the Cross-Disorder Group of the Psychiatric Genomics Consortium, and was funded by the US National Institutes of Health and a number of grants from other government agencies.

The study was published in the peer-reviewed journal The Lancet. The study was widely covered in the global media, but the story broke slowly in the UK, first by BBC Radio 4’s Today programme, then Sky News. Other UK outlets have since picked up the news. This story was based on a complex piece of research and was covered simply but accurately in the news.

What kind of research was this?

This was a genome-wide association study of five conditions: autism spectrum disorders, attention deficit hyperactivity disorder (ADHD), major depressive disorder, bipolar disorder and schizophrenia.

These five conditions are generally classified as either starting in childhood (childhood onset – autism, ADHD) or in adulthood (adult onset – depression, bipolar disorder, schizophrenia). There are currently no medical tests for any of these conditions. Instead, they are diagnosed according to the occurrence and impact of distinct sets of symptoms.

It is uncertain what precisely causes any of these conditions. The consensus is that a combination of genetic, biological and environmental factors contributes to their development.

This research examines possible genetic factors and how they may be shared across these five disorders.

What did the research involve?

The researchers analysed genetic data from more than 30,000 people with autism, ADHD, depression, bipolar disorder or schizophrenia, and compared it with the genetic sequences of more than 27,000 people who did not have these conditions. All were of European ancestry.

They carried out several distinct analyses in order to determine whether specific genetic variations were associated with these disorders, and whether any of these variations were linked to multiple disorders.

The human genome is the entire sequence of information contained within our DNA. This sequence is made up of strings of molecules called nucleotides, which are the building blocks of DNA. These nucleotides can develop into distinct variants known as single-nucleotide polymorphisms (SNPs). Certain types of SNPs are thought to have a significant effect on human health.

In this study, researchers first analysed genome-wide SNP data to determine if any were associated with the five conditions being studied.They then ran several additional analyses to determine whether these variations were associated with multiple disorders (called cross-disorder associations), and whether these genetic risk factors overlapped across the five conditions.

The researchers also assessed which genes these variations were located near to or in. This is so they could understand which genes may be responsible for the associations seen and which particular biological process (or pathways) they play a role in. This could potentially provide clues as to how SNPs could contribute to these mental health conditions.

The researchers also looked at a number of SNPs that previous studies found were associated with bipolar disorder and schizophrenia.

What were the basic results?

The researchers analysed genetic data from 33,332 individuals with one of the five conditions, as well as from 27,888 controls. They carried out initial analyses that supported the view that a large number of genetic variants each have a small effect on the risk of developing the five disorders.

In their main analysis, the researchers found that specific variations (SNPs) in four regions of the genetic code were significantly associated with these conditions. They then looked at whether the variations in these four regions increased the risk of each condition and the size of the effect.

They found that three of the variations seemed to have a similar effect in all five conditions. The fourth variation showed significant variation in effect across the disorders, with its effects most apparent in bipolar disorder and schizophrenia.

Some of the variations that were linked to bipolar disorder or schizophrenia in previous analyses also showed evidence of an effect across some of the other conditions. However, the evidence for these associations was not as strong as for the other four variants they identified.

The researchers found evidence that some conditions share common genetic risk factors, with the genetic variations associated with schizophrenia overlapping with both depression and bipolar disorder. The results also suggest overlap between autism, schizophrenia and bipolar disorder, but this link was not as strong.

They also found that variations in two of the four main regions identified were linked to genes involved in controlling the flow of calcium through cell membranes in response to electrical signals. This process plays an important part in nerve cell signalling and signalling within cells.

Previous studies have found associations between bipolar disorder, schizophrenia and major depressive disorder and the SNPs linked to these genes. SNPs linked to other genes that play a role in calcium flow across membranes were also found to show evidence of association with the five conditions. Overall, this suggests that this biological process could be important in the development of these mental or behavioural conditions.

How did the researchers interpret the results?

The researchers concluded that five common psychiatric conditions traditionally considered to be clinically distinct may in fact share genetic risk factors.

Conclusion

This study suggests that autism, ADHD, clinical depression, bipolar disorder and schizophrenia may have common genetic risk factors. The five conditions examined in this study were selected on the basis of the availability of a large genetic data set.

It is unclear at this stage whether other relatively common mental health conditions (such as anxiety disorder or obsessive compulsive disorder) are also affected by these genetic variations, or whether there is overlap with other conditions.

Perhaps most importantly, these variations cannot on their own predict or explain the development of autism, ADHD, depression, bipolar disorder or schizophrenia. The researchers point out that – as with almost all genome-wide association studies of complex conditions – the effect of the individual variations identified in these four regions was small, and cannot predict or diagnose these mental health conditions.

However, the researchers report that evidence from a variety of research, “including that from clinical, epidemiological and molecular genetic studies, suggests that some genetic risk factors are shared between neuropsychiatric disorders.”

They suggest that this study adds to such evidence, and provides “insights into the shared causation of psychiatric disorders”. These insights are, specifically, that changes in calcium signalling could be a fundamental biological mechanism “contributing to a broad vulnerability to psychopathology”.

This research may provide early clues about the role of a shared mechanism in the development of several psychiatric conditions, and may eventually help clinicians understand how and why individual patients develop some mental health conditions. Such an understanding may eventually lead to a new generation of drug treatments for these conditions.

However, in the light of this report it would be simplistic to assume that mental health conditions such as depression or schizophrenia are purely genetic – environmental factors are also thought to play a part.

In the same vein, treatment for these conditions does not just involve drugs. Talking therapies such as cognitive behavioural therapy (CBT) have been proven to be effective in many cases.

 

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