January 14, 2021
2 min read
Perry reports receiving grants from the National Institute for Health Research during the conduct of the study. Please see the study for all other authors’ relevant financial disclosures.
Changes in insulin sensitivity and adiposity beginning in childhood appeared to have disorder-specific links to psychosis and depression, according to study results published in JAMA Psychiatry.
Benjamin I. Perry
“It is now well understood that people with psychosis and depression are more likely than the general population to suffer from disorders of glucose-insulin homeostasis, such as insulin resistance or type 2 diabetes, and obesity,” Benjamin I. Perry, MRCPsych, of the Inflammation and Psychiatry Research Group at the University of Cambridge, told Healio Psychiatry. “However, the majority of previous research has been cross-sectional, and/or has included people who have already received a psychiatric diagnosis. This means that it has not been possible to disentangle the direction of association (ie, what comes first, the disruption to glucose-insulin homeostasis or the psychiatric diagnosis).”
Moreover, Perry noted that prior research mostly included single point measurements of cardiometabolic markers, despite repeat measures providing much greater resolution into potential underlying biological pathways.
Perry and colleagues sought to determine whether longitudinal associations existed between specific developmental trajectories of fasting insulin levels and BMI from early childhood and psychosis and depression among young adults. They analyzed data for fasting insulin levels of 5,790 individuals and for BMI of 10,463 individuals, all of whom were aged 1 to 24 years and included in the prospective Avon Longitudinal Study of Parents and Children, conducted in Britain.
They used BMI and fasting insulin level data for growth mixture modeling to delineate developmental trajectories, and they assessed associations with psychosis and depression. Exposures included fasting insulin levels at 9, 15, 18 and 24 years, as well as BMI at 1, 2, 3, 4, 7, 9, 10, 11, 12, 15, 18 and 24 years.
As potential confounders, the researchers examined data on sex, race/ethnicity, paternal social class, childhood emotional and behavioral problems and cumulative scores of sleep problems, average calorie intake, physical activity, smoking and alcohol and substance use during childhood and adolescence. They also assessed psychosis risk based on definite psychotic experiences, psychotic disorder, at-risk mental state status and negative symptoms score, as well as depression risk according to the computerized Clinical Interview Schedule-Revised, at 24 years.
Results showed three distinct trajectories for fasting insulin levels and five for BMI; all were differentiated by mid-childhood. Perry and colleagues noted an association between the persistently high fasting insulin level trajectory and a psychosis at-risk mental state adjusted OR [aOR] = 5.01; 95% CI, 1.76-13.19) and psychotic disorder (aOR = 3.22; 95% CI, 1.11-9.9) but not depression (aOR = 1.38; 95% CI, 0.75-2.54). Further, they observed an association between a puberty-onset major BMI increase and depression (aOR = 4.46; 95% CI, 2.38-9.87) but not psychosis (aOR = 1.98; 95% CI, 0.56-7.79).
“Traditionally, the received wisdom has been to consider that the psychiatric diagnosis comes first, and the physical health problems occur completely as a result of lifestyle factors (smoking, diet, exercise), health care inequalities or adverse effects of psychotropic medication,” Perry said. “Although these factors remain highly important and represent malleable targets to address physical comorbidity, our results suggest that subtle changes to cardiometabolic function could be detectable long before a diagnosis of psychosis and depression in adulthood. Our results underscore the vital importance that all young people presenting with psychosis or depression also receive a full and comprehensive assessment of their physical health.
“Early assessment and intervention of both the psychiatric and physical health of these individuals is the best way to improve long term outcomes, and help to close the mortality gap,” Perry added.