Insulin Levels, BMI Trajectory Help Predict Risk of Mental Health Disorders Later in Life

Benjamin Perry, PhD

While multiple studies have linked glycemic variability in midlife to cognitive decline in diabetics, new research from the University of Cambridge suggests high insulin levels and BMI changes in childhood could signal a greater risk of psychosis and depression as a young adult in otherwise healthy patients.

An analysis of data from within the Avon Longitudinal Study of Parents and Children (ALSPAC), investigators suggest results outline the importance of diet and physical activity throughout life as avenues to modify risk of developing psychosis, depression, or other mental health disorders later in life.

"The general assumption in the past has been that some people with psychosis and depression might be more likely to have a poor diet and lower levels of physical exercise, so any adverse physical health problems are a result of the mental disorder, or the treatment for it," said lead investigator Benjamin Perry, PhD, of the University of Cambridge Department of Psychiatry, in a statement. "In essence, the received wisdom is that the mental disorder comes first. But we've found that this isn't necessarily the case, and for some individuals, it may be the other way around, suggesting that physical health problems detectable from childhood might be risk factors for adult psychosis and depression."

To explore how developmental trajectories of fasting insulin levels and BMI during early life were associated with risks for psychosis and depression later in life, investigators designed their study as an analysis of data from within ALSPAC. A birth cohort study enrolling ALSPAC enrolled more than 14,000 live births born between April 1, 1991 and December 31, 1992.

During ALSPAC, measurements of fasting insulin levels were recorded at ages 9, 15, 18, and 24 years. A total of 5790 participants had data related to fasting insulin levels and were included in the analyses. BMI measurements were recorded at 1, 2, 3, 4, 7, 9, 10, 11, 12, 15, 18, and 24 years. A total of 10,463 participants had data available for BMI. Using the data from the aforementioned patient groups, investigators created 3 distinct trajectories for fasting insulin levels and 5 distinct trajectories for BMI.

For the purpose of analysis, investigators used data related to 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 as confounders in adjusted analyses. The primary outcomes of interest were psychosis risk and depression risk at 24 years. Of note, psychosis risk was defined by psychotic experiences, psychotic disorder, at-risk mental state status, and negative symptom score while depression risk was measured using the computerized Clinical Interview Schedule-Revised.

Upon analysis, investigators found individuals with persistently high fasting insulin levels were associated with a psychosis at-risk mental state (aOR, 5.01; 95% CI, 1.76-13.19) and psychotic disorders (aOR, 3.22; 95% CI, 1.11-9.90), but not depression (aOR, 1.98; 95% CI, 0.56-7.79). When assessing BMI trajectories, results indicated a puberty-onset major increase in BMI as associated with an increased risk of depression (aOR, 4.46; 95% CI, 2.38-9.87) but not psychosis (aOR, 1.98; 95% CI, 0.56-7.79).

"These findings are an important reminder that all young people presenting with mental health problems should be offered a full and comprehensive assessment of their physical health in tandem with their mental health," added Perry. "Intervening early is the best way to reduce the mortality gap sadly faced by people with mental disorders like depression and psychosis.”

This study, “Longitudinal Trends in Childhood Insulin Levels and Body Mass Index and Associations With Risks of Psychosis and Depression in Young Adults,” was published in JAMA Psychiatry.