Changing forms of Unreason

The changes in public perception of mental health topics have been very clear in recent years where once a never-to-be-discussed topic has now become widely reported, discussed and recognised. The number of widely shared and heard discussions about anxiety and depression has been further increased by the coronavirus pandemic. This change can be witnessed everywhere starting from the individual level, where people are becoming more vocal sharing their personal mental health stories, to community and societal level where universities, workplaces and the government are implementing more impactful mental health care policies.

What was known to be a taboo topic not so long ago, mental illness now has become more visible, more acceptable, and more accepted (or so it seems). Mental health has gone mainstream.

That is not to say that the stigma is gone and there is no more work left to do. Ultimately, this rise in public interest can be seen as a contributing factor to the increasing numbers of patients diagnosed with a mental health disorder, which was even termed as a ‘tsunami of mental illness’ by Prof Wendy Burn, president of the Royal College of Psychiatrists. Indeed, if increasing awareness has resulted in more diagnoses, this must be recognised  as an ultimate victory (as people are seeking for the help they need). However, a possible contributor to the rising numbers of mental health sufferers could be the diagnostic procedures.

A tricky part of the mental health specialist’s duties is patient diagnosis and there are several reasons why. According to the modern psychiatric disorders’ classification, there is a lot of overlap between the symptoms of the mental health disorders. Furthermore, the somewhat stringent disease classification criteria fails to reflect the reality of the patients as illustrated by a recent survey where patients suffering from depression, panic or post-traumatic stress disorders appeared to cut across multiple diagnostic categories as if those categories were not there. It has become clear that the methods of diagnosis play a pivotal role.

One of the first methods in history used to recognise mental illness can be found in religious texts. In these texts a mental disorder was treated as (nothing short of) a demonic possession where the root of the malady was evil itself.

Later, mental disorders became increasingly recognised as problems requiring medical intervention. The proposed causes of the illnesses included ‘the accumulation of bile’ to which the treatment involved ‘relieving the patient of the fluids’. Eventually, the diseases of the mind (termed as unreason in the 20th century by the philosopher Michel Foucault) started to be treated as a part of general illnesses. Nevertheless, to this day, no quantitative tests are implemented in the mental health specialist’s routine used to diagnose patients, and the diagnosis vastly depends on questionnaires. Although this is the best of what is available, such diagnosis has even been labelled as ‘scientifically meaningless’ and (un)surprisingly inaccurate as more than 50% of patients are initially misdiagnosed.

Misdiagnosis occurs not only due to the lack of quantitative tests, but also due to the way diseases are classified. It seems that now psychiatry is undergoing a paradigm shift. It is moving away from the acceptance of distinct diagnoses to a representation of psychiatric illness that crosses diagnostic boundaries. Such changes could improve the diagnostic accuracy, lead to novel approaches to treatments and help in discovering underlying causes of the disorders. This is of utmost importance for developing accurate diagnostic approaches. Currently, the lack of the quantitative tests stems from many unknowns in causes of mental illnesses. Nonetheless, scientists believe that there is a way, and that way is genomics.

It’s all in your head genes?

Emerging research now allows us to touch the tangible remnants of the unreason. In 2021, a genome-wide association study (GWAS) of health records of 1.2 million people from four separate data banks identified 178 gene variants linked to depression, a disorder that will affect around one in five people during their lifetimes. This and other similar studies are moving scientists closer to pointing out the causes and contributing factors of the mental health disorders. Furthermore, it is also pivotal for developing genetics-based diagnostic tests.

Finally, the published data can also be useful for developing treatments as recognising the functions of the identified different genetic variants can be used for target discovery. One of the potential drug candidates is riluzole, which is currently used for treating amyotrophic lateral sclerosis. Such drug repurposing can help put forth new treatments faster, as the drugs are already approved for the market. In addition, it will also be useful for tailoring treatments to patients as it is based on genetic variations.

The term pharmacogenomics (which first appeared almost 70 years ago) is used to describe the approach where genomics data is used to inform drug design process. Companies utilising the opportunity to connect pharmacogenomics with mental disorders are already on the market producing quantitative diagnostic tests. Another study supporting genetic predisposition to certain mental disorders comes from the University of Oxford. The study aims to demonstrate that our genes influence the way our brains are wired up, making us more (or less!) vulnerable to mental health conditions. A psychotherapist Dr. Margret Cochran also supports this notion and believes that the ’Mental illness is inherited and is genetically based. All of it – depression, anxiety, schizophrenia, personality disorders – are inheritable’.

Some scientists harbour an opposing view. A recent study of 50,000 patients at UCL failed to find any links between genetics and mental disorders. The lead scientist Prof David Curtis argues that no gene seems to be more important than the other in the development of the mental illnesses. Studies demonstrating mental health disease heritability have been disproven before, as it appears that the influence of the environmental factors on the way genes work and are expressed has been underestimated and may be more important that genes themselves. Whilst this is great news for the families which suffer from the mental health disorders, this clouds the way towards designing quantitative tools for diagnosis.

Changing the forms of Unreason

Given the immense changes in the mental health field starting from scientific discoveries to the public perception, one wonders what the future holds. A different approach towards researching the phenomenon of mental disorders could involve the reclassification of the diseases. The change in the scientific classification is needed due to the recently published findings. It has now been demonstrated that brains that are ‘wired up’ in a particular way are associated with not just one but a whole range of mental health conditions including schizophrenia, depression, anxiety, and bipolar disorder.

Called a brain ‘vulnerability network’, this pattern of connections may help us to understand why different mental health conditions seem to run in the same families and explain what makes a patient with one psychiatric disorder more likely to be diagnosed with another. This vulnerability network also shows how the genetic risks for various psychiatric illnesses arise through a common neurobiological root.

Therefore, instead of hoping to find a single gene or a genetic variant involved in psychiatric disorders, it appears that we should be looking for patterns or networks instead. The change in the way we approach studying psychiatric disorders therefore might not only hold the key in identifying genetic causes but will also help design accurate quantitative tools for disease diagnosis. In addition, all common disorders such as dementias, cancer and cardiovascular disorders have been shown to have some genetic predisposition. The future remains hopeful for the studies of psychiatric genetics. After the long-winded history of diagnosing and treating mental health disorders, novel, accurate and quantitative evidence-based diagnostic tools seem to be as close as ever.