Pediatric Insulin Levels, BMI Linked to Adult Psychosis and Depression

Benjamin Perry, MRCPsych

A new study suggested that the cardiometabolic comorbidity of psychosis and depression in adults may have origins in early life.

For example, the investigators noted an association between disrupted insulin sensitivity from mid-childhood and adult psychosis. BMI increases during the onset of puberty were linked to depression.

The study, led by Benjamin Perry, MRCPsych, Department of Psychiatry, University of Cambridge School of Clinical Medicine, analyzed longitudinal trends in fasting insulin levels and BMI among a pediatric cohort up to the age of 24.

“Genetic studies have indicated associations of BMI with depression and fasting insulin levels with schizophrenia,” the Perry and team wrote. “However, to our knowledge, no studies have examined whether fasting insulin level and BMI trajectories from childhood are associated with adult psychosis and depression.”

Evaluating Cardiometabolic Comorbidities, Psychosis, and Depression

To measure these associations, the investigators collected data from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort, a prospective study that included 14,975 individuals, most (n = 14,063) of which were recruited before delivery.

Using an ultrasensitive automated microparticle enzyme immunoassay, the team measured fasting insulin levels at ages 9 (n = 894), 15 (n = 3483), 18 (n = 3286), and 24 (n = 3253).

BMI was calculated at ages 1 (n = 1036), 3 (n = 1050), 4 (n = 1018), 7 (n = 8200), 9 (n = 7633), 10 (n = 7465), 11 (n = 7100), 12 (n = 6704), 15 (n = 5415), 18 (n = 5061), and 24 (n = 3975).

At age 24, participants were assessed for risk of psychosis through measurements of definite psychotic experiences, psychotic disorder, at-risk mental state status, and negative symptom score.

Depression risk was measured using the computerized Clinical Interview Schedule-Revised.

“For assessment of potential confounders, we included sex at birth, race/ethnicity, paternal social class, childhood emotional and behavioral problems (measured using the Strength and Difficulties Questionnaire at age 7 years), and cumulative scores of smoking, physical activity, alcohol use, substance use, sleep problems, and average calorie intake between ages 7 and 24 years,” the investigators wrote.

All data was analyzed between July 15, 2019 – March 24, 2020.

As such, data on fasting insulin levels was available for 5790 participants (54.1% female). Data on BMI was available for 10,463 participants (51.0% female).

The team noted that a persistently high fasting insulin level trajectory was associated with a psychosis at-risk mental state (OR, 5.01; 95% CI, 1.76-13.19) and psychotic disorder (OR, 3.22; 95% CI, 1.11-9.90), but not depression (OR, 1.38; 95% CI, 0.75-2.54).

Fasting insulin level trajectories that deviated from a stable average were associated with lower social class, family history of cardiometabolic disease, lower physical activity, and smoking in adolescence and early adulthood.

In terms or BMI, an increase noted during puberty was associated with depression (OR, 4.46; 95% CI, 2.38-9.8) but not psychosis (OR, 1.98; 95% CI, 0.56-7.79).

Compared with stable average BMI, deviating trajectories were associated with lower social class, family history of cardiometabolic disease, more perinatal stressful life events, lower physical activity, and smoking in adolescence and early adulthood compared with the stable average trajectory.

“Although residual confounding may be an issue, our results suggest that these cardiometabolic markers could be among shared risk factors and indicators for adult cardiometabolic and psychiatric disorders and may represent novel targets for prevention and treatment of cardiometabolic disorders in people with psychosis and depression,” Perry and colleagues concluded.

They acknowledged a need for replication with larger sample sizes and using additional analyses, such as mendelian randomization analysis, that can identify potentially unconfounded associations.

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