Evaluation of Brain-Body Health in Individuals With Common Neuropsychiatric Disorders

Abstract

Importance: Physical health and chronic medical comorbidities are underestimated, inadequately treated, and often overlooked in psychiatry. A multiorgan, systemwide characterization of brain and body health in neuropsychiatric disorders may enable systematic evaluation of brain-body health status in patients and potentially identify new therapeutic targets.

Objective: To evaluate the health status of the brain and 7 body systems across common neuropsychiatric disorders.

Design, setting, and participants: Brain imaging phenotypes, physiological measures, and blood- and urine-based markers were harmonized across multiple population-based neuroimaging biobanks in the US, UK, and Australia, including 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; and Human Connectome Project-Aging. Cross-sectional data acquired between March 2006 and December 2020 were used to study organ health. Data were analyzed from October 18, 2021, to July 21, 2022. Adults aged 18 to 95 years with a lifetime diagnosis of 1 or more common neuropsychiatric disorders, including schizophrenia, bipolar disorder, depression, generalized anxiety disorder, and a healthy comparison group were included.

Main outcomes and measures: Deviations from normative reference ranges for composite health scores indexing the health and function of the brain and 7 body systems. Secondary outcomes included accuracy of classifying diagnoses (disease vs control) and differentiating between diagnoses (disease vs disease), measured using the area under the receiver operating characteristic curve (AUC).

Results: There were 85 748 participants with preselected neuropsychiatric disorders (36 324 male) and 87 420 healthy control individuals (40 560 male) included in this study. Body health, especially scores indexing metabolic, hepatic, and immune health, deviated from normative reference ranges for all 4 neuropsychiatric disorders studied. Poor body health was a more pronounced illness manifestation compared to brain changes in schizophrenia (AUC for body = 0.81 [95% CI, 0.79-0.82]; AUC for brain = 0.79 [95% CI, 0.79-0.79]), bipolar disorder (AUC for body = 0.67 [95% CI, 0.67-0.68]; AUC for brain = 0.58 [95% CI, 0.57-0.58]), depression (AUC for body = 0.67 [95% CI, 0.67-0.68]; AUC for brain = 0.58 [95% CI, 0.58-0.58]), and anxiety (AUC for body = 0.63 [95% CI, 0.63-0.63]; AUC for brain = 0.57 [95% CI, 0.57-0.58]). However, brain health enabled more accurate differentiation between distinct neuropsychiatric diagnoses than body health (schizophrenia-other: mean AUC for body = 0.70 [95% CI, 0.70-0.71] and mean AUC for brain = 0.79 [95% CI, 0.79-0.80]; bipolar disorder-other: mean AUC for body = 0.60 [95% CI, 0.59-0.60] and mean AUC for brain = 0.65 [95% CI, 0.65-0.65]; depression-other: mean AUC for body = 0.61 [95% CI, 0.60-0.63] and mean AUC for brain = 0.65 [95% CI, 0.65-0.66]; anxiety-other: mean AUC for body = 0.63 [95% CI, 0.62-0.63] and mean AUC for brain = 0.66 [95% CI, 0.65-0.66).

Conclusions and relevance: In this cross-sectional study, neuropsychiatric disorders shared a substantial and largely overlapping imprint of poor body health. Routinely monitoring body health and integrated physical and mental health care may help reduce the adverse effect of physical comorbidity in people with mental illness.

Figure 1.. Brain and Body Health Scores in Neuropsychiatric Disorders Stratified by Organ System

Organ and system health scores were computed for each organ system (2 brain and 7 body) and for each individual. A score of 0 indicates healthy, normal organ function (ie, median score across healthy comparison individuals), and scores below 0 suggest deterioration of organ health, controlling for age and sex. Radial axes show the mean of estimated organ and system health scores across individuals within each neuropsychiatric disorder and healthy comparison individuals. An overall body health score was estimated using all body phenotypes. Distributions of estimated organ and system health scores across individuals in each group are shown in eFigure 6 in Supplement 1.

Figure 2.. Brain and Body Health Scores in Neuropsychiatric Disorders Stratified by Diagnosis Group

Radial plots show the mean estimated organ health scores within each neuropsychiatric disorder. Organ systems in each plot were organized counterclockwise according to the mean health score from the smallest to the largest value.

Figure 3.. Accuracy of Diagnostic and Transdiagnostic Disease Classification

A, A logistic regression model was trained to classify an individual’s diagnostic status, including specific diseases and healthy control. Classification models were established for each organ system, using organ-specific phenotypic deviation scores. Each row represents 1 target disease group, and icons are positioned to indicate the classification accuracy, as quantified by the area under the receiver operating characteristic curve (AUC). B, A logistic regression model was trained to classify an individual’s diagnostic status between disease pairs. Each row represents 1 target disease group, and icons are positioned to the average accuracy in differentiating each disease group from all the other groups.