Is 'mental illness' in the mind, or the body... or both?
People with so-called mental illness are actually sicker in their bodies than in their brains. What does this mean for diagnosis and treatment?
In last week's post, Worried sick, I briefly mentioned a study which examined markers of both brain and body health in people diagnosed with any of four neuropsychiatric conditions, and found that they had greater deviations from healthy controls in markers of body health – most notably in their metabolic, hepatic, and immune systems – than in markers of brain health.
This study, titled 'Evaluation of Brain-Body Health in Individuals With Common Neuropsychiatric Disorders', is interesting both for what it reveals about the physical health of people diagnosed with (so-called) mental illness, and what it fails to discuss. Let's dig into it together.
Researchers from a number of Australian universities and medical research centres obtained biometric data on brain and body health from almost 86 000 adults diagnosed with one or more "common neuropsychiatric disorders" – schizophrenia, bipolar disorder, depression and generalised anxiety disorder – and a roughly equal number of healthy controls (i.e. people who had never had any of these diagnoses), matched for age and sex.
All participants were enrolled in one of the following population-based neuroimaging biobanks based in the US, UK, and Australia:
UK Biobank
Australian Schizophrenia Research Bank
Australian Imaging, Biomarkers, and Lifestyle Flagship Study of Ageing
Alzheimer’s Disease Neuroimaging Initiative
Prospective Imaging Study of Ageing
Human Connectome Project–Young Adult
Human Connectome Project–Aging.
The researchers used brain imaging data on grey matter and white matter volume, obtained from magnetic resonance imaging (MRI) scans of participants without any neuropsychiatric illness or other serious medical conditions, to establish sex-specific normative reference ranges for brain health across the adult life span.
Likewise, they used data from physical assessments and blood and urine sample assays of UK Biobank participants, to establish normative ranges for biomarkers of the health of seven body systems: pulmonary, musculoskeletal, kidney, metabolic, hepatic, cardiovascular, and immune.
In all, the researchers established normative reference ranges across the adult life span for 203 imaging, blood, urine, and physiological markers of brain and body health.
Then they compared the brain scans and physiological health markers of people diagnosed with schizophrenia, bipolar disorder, depression and generalised anxiety disorder, to the norms they had established for the healthy controls. What they found was fascinating, and enormously challenging to the typical framing of 'mental illness': People diagnosed with any of the four neuropsychiatric illnesses, deviated more from the healthy reference ranges in markers of body health than in brain health. That is, their bodies were more obviously sick than their brains.
Looking first at markers of body health, the researchers reported:
"We found that all organ-specific health scores were on average significantly lower in individuals with neuropsychiatric disorders compared to age- and sex-matched healthy peers."
Evaluation of Brain-Body Health in Individuals With Common Neuropsychiatric Disorders
The metabolic, hepatic (liver), immune and kidney systems showed the most deviation from healthy norms. The poorest body health scores were found in schizophrenics, followed by people with bipolar disorder, depression, and generalised anxiety disorder.
Turning to markers of brain health, "subtle structural brain changes" were noted in people diagnosed with bipolar disorder, depression and generalised anxiety disorder, but the researchers rated their brain health as only marginally worse than that of healthy controls. Schizophrenics had the poorest brain health, but the differences between them and the healthy controls were described as "small to moderate".
In summary,
"Body health was on average poorer than brain health in these patients, which may be partly explained by physical comorbidities."
Evaluation of Brain-Body Health in Individuals With Common Neuropsychiatric Disorders
The researchers were able to develop diagnostic classification algorithms that accurately differentiated people with schizophrenia, bipolar disorder, depression, or generalised anxiety disorder from healthy controls, on the basis of differences in markers of body health. To their own evident surprise, these were more accurate than classification algorithms based on brain imaging. However, brain-based diagnostic algorithms outperformed body-based classification systems when it came to differentiating between neuropsychiatric diagnoses (e.g. distinguishing a person suffering from schizophrenia, from a person with bipolar disorder).
Why are people with neuropsychiatric diagnoses so physically unwell?
The researchers decry the lack of attention paid to the body health of people diagnosed with (so-called) mental illness, despite the known high rates of physical comorbidities:
"Mental illness is associated with higher rates of chronic physical illness, including coronary heart disease, obesity, and diabetes,1,2 compared to the general population. This contributes substantially to the global health and economic burden due to increased morbidity, disability, and mortality.3,4 Yet in psychiatric care and services, physical health has been neglected and inadequately managed for decades."
Evaluation of Brain-Body Health in Individuals With Common Neuropsychiatric Disorders
They blame a number of factors for this neglect:
"Poor physical health in patients is likely underestimated due to existing disparities in health care for people with mental illness, such as lack of access to adequate primary care,7 diagnostic overshadowing,8,9 and difficulties with acknowledging10 and reporting medical problems for some patients.11,12"
Evaluation of Brain-Body Health in Individuals With Common Neuropsychiatric Disorders
And finally, they summarise the implications of their findings as follows:
"Meaning Management of serious neuropsychiatric disorders should acknowledge the importance of poor physical health and target restoration of both brain and body function."
Evaluation of Brain-Body Health in Individuals With Common Neuropsychiatric Disorders
"Restoration of both brain and body function." Doesn't that sound marvellous? And completely antithetical to the theory and practice of orthodox medicine. Psychiatric medications are, as Dr Peter Breggin has described in great detail, brain-disabling. And as I discussed in Stop calling them ‘side effects’, the vast majority of pharmaceuticals prescribed for physical ailments 'work' by interfering with body functions, not "restoring" them.
Furthermore, the study authors failed to mention the fact that psychiatric medications are well known to cause derangements in physical function, including in the body systems which they identified as furthest from healthy norms in participants with neuropsychiatric diagnoses (metabolic, liver, immune and kidney). For example:
Antipsychotic drugs, which are used to treat the symptoms of schizophrenia, bipolar disorder, and increasingly, major depression, cause metabolic syndrome (weight gain, high triglycerides, and elevated insulin, glucose, and low-density lipoprotein cholesterol levels) and type 2 diabetes.
Selective serotonin reuptake inhibitors (SSRIs), which are the most frequently prescribed drugs for people with depression and anxiety and are also frequently taken by people with schizophrenia and bipolar disorder, are also linked to increased risk of developing metabolic syndrome.
Certain antipsychotics have been linked to liver toxicity. Chlorpromazine, clozapine, and olanzapine are the most dangerous, while quetiapine and risperidone pose a moderate risk.
Antidepressants cause mild elevation of serum aminotransferase levels (an indicator of liver damage) in 0.5−3 per cent of patients, and can induce hepatotoxicity, especially in elderly patients and those taking multiple drugs (which is very common for people diagnosed with neuropsychiatric conditions).
SSRIs exert a number of effects on the immune system, including suppressing the proliferation and activity of lymphocytes (key cells in the response to viral and bacterial infection, and cancer).
Second-generation antipsychotics are associated with an increased risk of developing chronic kidney disease.
I find it impossible to believe that the authors of this study are unaware of the voluminous research on adverse effects of psychiatric drug use. So why did they not even explore the possibility that at least some of the impaired body function that they identified in participants with neuropsychiatric diagnoses was actually iatrogenic (treatment-induced), rather than an intrinsic component of the (so-called) mental illness?
If I were the cynical type, I might suspect that at least some of the authors - especially those linked to QIMR Berghofer, which develops drug and biologic candidates for commercial release - are preparing the ground for the development of new, biologically-based, therapeutic agents for treatment of neuropsychiatric conditions. But who could be that cynical?
All that said, it is undeniably the case that so-called mental illness is not a discrete entity, confined to the minds of sufferers. It has, at the very least, biological correlates. For example,
"Abnormalities in glucose regulation were first reported in patients with schizophrenia and bipolar disorder prior to the introduction of antipsychotic medication, with early reports5,6 indicating a pattern of insulin resistance in untreated patients."
And, as I wrote in Rumination Inflammation, there is a strong link between systemic (body-wide) inflammation and depression:
"Levels of inflammatory chemicals such as tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), interleukin-10 (IL-10), and C-reactive protein (CRP) have been found to be elevated in depressed people (3), with the highest levels seen in those contemplating suicide (4)."
So we know that people with neuropsychiatric diagnoses also have significant impairments in their physical health; and we also know that at least some proportion of these impairments is intrinsic to their so-called mental illness, and some proportion to the adverse effects of the psychiatric drugs prescribed to them.
What other factors might be at play?
1. Poor diet quality
As I've discussed at length in many previous articles (e.g. The good news about depression – Part 1, Eat your way to better mental health?, Good mood food and The evidence is in: Eating better relieves depression), dietary practices have a major effect on our psychological well-being. Specifically, diets high in fruits, vegetables and other minimally-processed plant foods are protective against the development of depression and anxiety, and show promise in promoting remission in people who have already developed these conditions.
Unfortunately, people with neuropsychiatric diagnoses tend to have less healthful diets than people who don't, due to disordered eating behaviours, poor executive control, medication-driven appetite increase, and low food security linked to reduced income.
Which came first: the poor diet, or the neuropsychiatric condition? Or are they mutually reinforcing? My guess is the latter option. In any case, the same poor dietary quality associated with heightened risk for so-called mental illness is also a driver of bodily illness.
And that prompts an important question: is so-called mental illness simply a manifestation of disturbed physical function? I strongly suspect that it is, and that certain people are predisposed to manifest emotional, cognitive and psychological symptoms of disturbed physical function, as a consequence of...
2. Personality factors
Personality is highly heritable (i.e. linked to genes inherited from one's parents), quite stable across the life course, and associated with differences in neurotransmitter activity - that is, it has a neurobiological basis.
Certain personality traits are strongly linked to the development of neuropsychiatric illness; for example, low conscientiousness is linked to depression, anxiety, schizophrenia and bipolar. And personality is strongly associated with health status; for example, low conscientiousness is also associated with making food choices that result in poor nutritional quality, while high negative emotionality/emotional instability is linked to dysregulation of the hypothalamic-pituitary-adrenal axis.
Pulling all these threads together, and incorporating what I've observed in nearly 30 years of clinical practice, this is what I believe is happening:
Certain people are predisposed, by dint of genetic factors, to expressing personality traits that leave them vulnerable to developing neuropsychiatric illnesses, as well as to the behaviours (e.g. food choices and substance abuse) that exacerbate those illnesses.
Since personality has a neurobiological basis, it stands to reason that it influences biological function 'below the neck'. In other words, the same genetic factors that shape personality, also affect bodily functions and thereby influence health.
I speculate that in our ancestral hunter-gatherer environment, the negative impacts of these personality traits were mitigated by consumption of a micronutrient- and fibre-rich diet (with limited opportunities to overeat), daily physical activity, the absolute necessity to perform some type of productive work in order to survive, mandatory conformity with a healthy circadian rhythm (no artificial lighting!), and close social ties which ensured prompt attention to manifestations of psychological ill-health and made destructive self-isolation impossible.
Viewed through this lens, the neuropsychiatric illnesses that were the focus of the study I've discussed in this post, might be best characterised as manifestations of evolutionary mismatch. No drug, shock treatment or transcranial magnetic stimulation, or patentable biologic substance can 'fix' this mismatch. It requires a comprehensive Lifestyle Medicine approach, that incorporates attention to diet, exercise, circadian rhythm, social connection, cultivating a sense of purpose, resolution of past trauma, and usually, very careful tapering of brain- and body-impairing psychiatric medications. As far as I am aware, the "restoration of both brain and body function" that the authors call for, cannot be achieved by any other means.
Agree? Disagree? You know what to do!
Until the main profession people see for these problems (the medical one) starts to see people as WHOLE creatures, not part creatures whose mental and physical health are completely separate, there is no fixing this problem. One must always care the for WHOLE person if one wishes to see better results.
The medical profession has so much improvement to make. I don't know how they could've gotten to a much worse position than where they are now.
So many people's problems would be because of drug interactions. Let alone a poor diet and lack of exercise etc. So what do the docs do? Give people MORE drugs.
Not only that, they also need to look at TRENDS in people's health. As an example, seeing a blood result in the 'normal' zone but not seeing that figure has fallen a lot over the past year or two is yet another example of how they are not dealing with the 'whole' person.
Plus GPs really don't know very much about mental illness. Unless they have done extensive studies in the area (unlikely), they are some of the LAST health professionals we should be seeing for mental illness!
Thanks for another great article, Robyn. I'd like to share a conundrum of a situation.
My 37 year old daughter was unexpectedly diagnosed with bipolar disorder a decade ago. She is a musician and kinesiologist and yoga teacher. Diligent with diet and lifestyle, a meditator since her childhood (brought up in a yoga "cult" which, although I have long-since left, she chooses to regularly adhere to its practices). We have tried so many approaches, with excellent and committed practitioners including an integrative GP in Sydney (who incidentally advised agains the covid shots and wrote many exemptions - he was onto it in mid-2020), naturopaths, and a fantastic wholistic psychiatrist who uses supplements as well as judicious psychiatric drugs.
She has had every blood panel, hormone test, brain scan, genetic test we could find and we have done heaps of research. The most compelling explanation is that it seems there was some history of similar episodes in her paternal great-grandfather.
Despite all this, my daughter has had almost yearly relapses into mania and ended up in psychiatric wards in Sydney, Hong Kong, Amsterdam, London and more recently in rural Victoria. She doesn't have depression per se, but takes time to recover from the hospital admissions and the drugs administered to her there.
By and large my experiences with the more "allopathic" side of treatment and crisis teams etc have been good, and even interventions from the police have been reasonable. My daughter may not agree with this as she has been in the receiving end!
It has been a very difficult journey for her and our family. Mania is very hard for her to identify, as in the beginning it just feels like a very happy state, and can quickly build on itself. The most helpful protocol seems to be watching her circadian rhythms and prioritising sleep quality and quantity, regular lithium orotate (a "natural" and more bioavailable form of lithium), a heap of supplements, lifestyle management and occasional use of olanzapine. It appears that the olanzapine is vital to bring the mood down before it elevates, but is difficult for her to take as it does have side effects and she is very averse to allopathic medicine.
I'm sharing this as it can be very complex, and she doesn't fit into the typical patient profile. There is much less stigma around mental illness which is good, but we still come across the attitude from others such as "why doesn't she just stick to the meds?" Not helpful!
Thank you again, and I would be curious to hear your opinion.