Longitudinal Trends in Childhood Insulin Levels and Body Mass Index and Associations With Risks of Psychosis and Depression in Young Adults
Authors: Benjamin I. Perry, Jan Stochl, Rachel Upthegrove, Stan Zammit, Nick Wareham, Claudia Langenberg, Eleanor Winpenny, David Dunger, Peter B. Jones, Golam M. Khandaker
Journal: JAMA Psychiatry (2021)

<h3>Importance</h3> Cardiometabolic disorders often occur concomitantly with psychosis and depression, contribute to high mortality rates, and are detectable from the onset of the psychiatric disorders. However, it is unclear whether longitudinal trends in cardiometabolic traits from childhood are associated with risks for adult psychosis and depression. <h3>Objective</h3> To examine whether specific developmental trajectories of fasting insulin (FI) levels and body mass index (BMI) from early childhood were longitudinally associated with psychosis and depression in young adults. <h3>Design, Setting, and Participants</h3> A cohort study from the Avon Longitudinal Study of Parents and Children, a prospective study including a population-representative British cohort of 14 975 individuals, was conducted using data from participants aged 1 to 24 years. Body mass index and FI level data were used for growth mixture modeling to delineate developmental trajectories, and associations with psychosis and depression were assessed. The study was conducted between July 15, 2019, and March 24, 2020. <h3>Exposures</h3> Fasting insulin levels were measured at 9, 15, 18, and 24 years, and BMI was measured at 1, 2, 3, 4, 7, 9, 10, 11, 12, 15, 18, and 24 years. 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 in childhood and adolescence were examined as potential confounders. <h3>Main Outcomes and Measures</h3> Psychosis risk (definite psychotic experiences, psychotic disorder, at-risk mental state status, and negative symptom score) depression risk (measured using the computerized Clinical Interview Schedule–Revised) were assessed at 24 years. <h3>Results</h3> From data available on 5790 participants (3132 [54.1%] female) for FI levels and data available on 10 463 participants (5336 [51.0%] female) for BMI, 3 distinct trajectories for FI levels and 5 distinct trajectories for BMI were noted, all of which were differentiated by mid-childhood. The persistently high FI level trajectory was associated with a psychosis at-risk mental state (adjusted odds ratio [aOR], 5.01; 95% CI, 1.76-13.19) and psychotic disorder (aOR, 3.22; 95% CI, 1.29-8.02) but not depression (aOR, 1.38; 95% CI, 0.75-2.54). A puberty-onset major increase in BMI was associated with depression (aOR, 4.46; 95% CI, 2.38-9.87) but not psychosis (aOR, 1.98; 95% CI, 0.56-7.79). <h3>Conclusions and Relevance</h3> The cardiometabolic comorbidity of psychosis and depression may have distinct, disorder-specific early-life origins. Disrupted insulin sensitivity could be a shared risk factor for comorbid cardiometabolic disorders and psychosis. A puberty-onset major increase in BMI could be a risk factor or risk indicator for adult depression. These markers may represent targets for prevention and treatment of cardiometabolic disorders in individuals with psychosis and depression.