Complex Impacts of Obesity on the Brains of People with Psychiatric Disorders
Obesity in individuals with bipolar disorder or schizophrenia is closely linked not only to higher mortality but also to worse progression of the psychiatric illness, lower response to psychiatric treatment, more frequent fatal outcomes (suicide), deterioration in cognitive functions, and structural brain damage. In his lecture at the XIV Congress of the Psychiatric Society of the Czech Medical Association J.E. Purkyně in Mikulov in June 2022, Professor Tomáš Hájek from Dalhousie University in Halifax, Canada, focused on these connections.
Increased Mortality
The prevalence of obesity has tripled worldwide since 1975. Patients with bipolar disorder (BP) or schizophrenia are almost 3 times more likely to be obese than the general population. Obesity is associated with an increased incidence of other conditions such as diabetes, hypertension, atherosclerosis, heart disease, liver steatosis, and malignant tumors, and it is a significant factor increasing the mortality of patients with psychiatric disorders, who die most frequently from cardiovascular diseases, just like the general population.
Worsening of Psychiatric Illnesses and Response to Treatment
In addition, it has been proven that obesity in BP patients is associated with more frequent disability, chronicity of the disease, rapid cycling, and other psychiatric comorbidities, especially anxiety disorders. Obese BP patients have more severe and harder-to-treat episodes, a greater number of previous depressive and manic episodes, and a more frequent history of suicide attempts.
In the acute treatment of mood disorders, with every 1 kg/m2 increase in body mass index (BMI), the likelihood of therapeutic response to lithium + valproate decreased by 7.5%. Obese patients in this study had a significantly lower likelihood of achieving remission than non-obese participants (odds ratio [OR] 0.35; 95% confidence interval [CI] 0.14–0.89). It was also found that achieving a response to lithium treatment in BP patients is associated with a lower incidence of glucose tolerance disorder, insulin resistance, and type 2 diabetes.
Impact on Cognitive Functions
Increased BMI values are associated with worsening cognitive functions, and obesity is one of the most significant factors in the development of dementia in both the general population and BP patients. In schizophrenia, the impact of obesity on cognition is smaller, probably because the basic disease itself already has an adverse effect on cognitive functions. The more pronounced impact of obesity on cognition is evident when metabolic syndrome is present. It is known that worsening cognitive functions adversely affects the psychosocial functioning of patients.
Protoplastic Effects of Obesity on the Brain
In addition to the heart, kidneys, eyes, and lower limbs, the brain is also a target organ of the adverse effects of obesity. Several studies have repeatedly shown that obesity is associated with overall or localized changes in the brain's gray matter. These changes are similar to those seen in BP or schizophrenia.
The ENIGMA study, conducted in 13 countries and including 2735 participants, showed diffusely reduced cortical thickness throughout the neocortex in obese individuals. Moreover, it was found that in obese patients with BP or schizophrenia, these brain structural changes are more pronounced than in non-obese individuals. This study also showed that obesity is associated with a larger volume of brain ventricles. The presence of obesity explained 20–50% of the association between BP and increased brain ventricle volume.
The Czech longitudinal study ESO assessed brain age and aging using MRI in individuals with the first psychotic episode. At the time of the first episode, brain age in patients was on average 3.4 years older than in controls (p = 0.010) and correlated with worse functioning according to the GAF scale (p = 0.041) and higher symptom scores according to the PANSS scale in schizophrenic patients (p = 0.005). During the subsequent 1.6-year period, the rate of brain aging was comparable to healthy controls. The rate of brain aging was not associated with diagnosis, clinical characteristics, illness severity, medication, or global functioning of the patient. The only variable that predicted accelerated brain aging was BMI – with every 1 kg/m2 increase, brain aging accelerated by 1 month per year.
Impact of Medication on Obese Psychiatric Patients
Researchers also sought to answer the question of whether obesity could be the cause of the adverse effects of obesogenic psychiatric medications (such as valproate or antipsychotics) on the brain. They found that the obesogenic effects of psychiatric medication may contribute to brain changes associated with psychiatric medication, but the influence of other variables cannot be ruled out.
Data analysis from 15 original studies showed that medication increasing insulin sensitivity significantly alleviates depression symptoms. The alleviation of depression was not related to the improvement in metabolic markers or weight loss.
Conclusion
High BMI values represent a risk factor for progressive worsening of brain and clinical parameters in patients with BP and schizophrenia. Additionally, high BMI is unfavorably associated with clinical parameters of psychiatric diseases, which current modalities can hardly influence (worsened cognitive functions, structural brain changes, or poorer functioning of the patient in everyday life). Therefore, obesity prevention and treatment are relevant not only in somatic medicine but, according to these findings, may also improve the outcomes of psychiatric disease therapy.
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Source: Hájek T. Waist and brain volume are closely related – the impact of obesity on the brains of people with bipolar disorder or schizophrenia. Symposium
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