Schizophrenia as whole-body disorder – the 100-year-old idea only now being proven

A study from researchers at King's College London is suggesting that schizophrenia is not just a disorder of the mind but is also associated with defined physiological changes across the whole body. The study hypothesizes that these physical symptoms are not secondary effects of the illness but, in fact, indications that schizophrenia is a whole-body disorder.

For some time, scientists have observed strong associations between schizophrenia and poor physical health. Those diagnosed with the condition tend to have significantly reduced life expectancies, dying up to 20 years earlier due to a variety of issues, including heart disease, diabetes and suicide.

It has generally been considered that these secondary health factors were the result of the mental health issues. Poverty, homelessness, smoking, and a variety of social problems, are all common factors often seen in those with schizophrenia, and considered to be primarily what leads to reduced physical health and a shorter life expectancy.

But there is a growing body of evidence that suggests these bodily alterations associated with schizophrenia may not be secondary effects but rather they are fundamental symptoms of the illness.

A new paper, from a team of researchers at King's College London, collected case-study data from 165 different studies to examine the physiological states of subjects at the point they were first diagnosed with the onset of schizophrenia. The hypothesis being that if many of these physiological effects are considered social byproducts of the condition then they shouldn't be significantly apparent at the early stages of the illness.

"We pooled data from multiple studies, examining markers of inflammation, hormone levels and heart disease risk factors, including glucose and cholesterol levels," explains Toby Pillinger, a researcher on the project. "We also pooled data from studies examining brain structure, levels of different chemicals within the brain, and markers of brain activity."

From a sample size of over 13,000 subjects, the analysis concluded that there are robust physiological alterations that can be identified at the point of what the researchers term, "first-episode psychosis." These included alterations in both cardiometabolic and immune parameters compared with a healthy control group.

The "whole body madness" prognosis

The idea that schizophrenia could be a whole-body condition is not a new one. Despite it being labeled an illness of the mind for much of the 20th century, over 100 years ago an influential German psychiatrist named Emil Kraepelin was convinced it was in fact a broader systemic condition, a "whole body madness."

In the late 19th century, the condition we currently call schizophrenia was termed "dementia praecox." Across multiple editions of Kraepelin's landmark scientific psychiatric manual Psychiatrie he comprehensively categorized the condition of dementia praecox. In his later years Kraepelin became obsessed with the idea that the condition was not a disease of the brain but actually a broader metabolic disease that affected the entire body, organs and all. Kraepelin also considered the psychological effects of conditions like dementia praecox to be symptoms of this broader disease, suggesting in 1919 that in the future we will find traces of the disease in the blood.

"The careful study of the processes of metabolism and blood chemistry will provide us with important clues to the characterization and delineation of natural disease groups," wrote Kraepelin, almost 100 years ago.

As the field of psychiatry progressed in the 1920s with Freud and Jung's theories taking hold, Kraepelin's work slipped into obscurity. His views on the physiological underpinnings of mental health disorders were overtaken by more modern psychoanalytic interpretations. The term schizophrenia slowly took hold as the dominant descriptor for the condition.

Before Kraepelin died in 1926 a colleague reported he was openly intolerant of Freud and Jung, and obsessed with the growing scientific field of serology, the close diagnostic analysis of blood. A century later, Kraepelin's ideas are now proving compellingly prescient as research is beginning to reveal that schizophrenia does indeed have broader bodily biomarkers that can be identified.

A study published in 2014 found that patients suffering from their first psychotic episode displayed significantly elevated levels of pro-inflammatory cytokines in their blood. As well as suggesting schizophrenia can be associated with immune system dysregulation, it noted this could be a potential blood-based biomarker to track the illness.

In fact, several studies are now starting to find connections between mental illness and inflammation, giving weight to hypotheses these conditions previously considered psychological may have strong physiological roots. A 2015 study found a correlation between depression and neuroinflammation, while a more recent study found a fascinating link between inflammation in the brain and suicidal thoughts.

But are these physical symptoms causes or consequences? It is here that more research needs to be done, and Toby Pillinger suggests three potential hypotheses that could account for these growing associations between brain and body effects in schizophrenia.

The condition could begin in the brain, and the physical disorders stem from these fundamental neurological alterations. Pillinger points to the way stress can elevate levels of cortisol in the body which subsequently results in a variety of negative physical effects as an example of this action.

Another possibility follows Kraepelin's ideas – the dysfunction originates in the body and that leads to deficits in the brain. New evidence associating gut bacteria with several psychological conditions such as depression and PTSD could suggest the origins of some mental health disorders may lie outside of the brain.

The final possibility suggested by Pillinger is that these brain and body symptoms are the result of a separate common risk factor. As an example, Pillinger refers to the hypothetical scenario of a pregnant mother suffering through a famine. This malnutrition results in a variety of systemic developmental dysfunctions for her child that both affect the infant's ultimate body and brain.

Despite being floated over a century ago, these ideas suggesting broader metabolic explanations behind mental health disorders are only just now being effectively scientifically investigated. Dramatic progressions in research technology and diagnostic techniques over the past few decades are allowing scientists to unlock new physiological associations between the body and brain. Hopefully this pioneering research will lead to the development of more effective treatments for the conditions that humanity has been struggling to define for centuries.

The new study was published in the journal Molecular Psychiatry.

Source: The Conversation