1. Persistently high fasting insulin levels were associated with psychosis and psychotic disorder later in life.
2. Major increases in body mass index during puberty were associated with increased risk of depression later in life, but not psychosis.
Evidence Rating Level: 2 (Good)
Cardiometabolic disorders often co-occur with schizophrenia and depression, which exacerbates declines in functional abilities, quality of life, and overall health outcomes. While some of these disorders are often attributed, in part, to lifestyle factors, there is evidence to suggest that first-episode psychosis may arise from altered glucose-insulin homeostasis in young, drug-naïve patients. This cohort study using repeated-measure data from the Avon Longitudinal Study of Parents and Children, a population-representative British dataset, chose individuals from ages 1 to 24 years with body mass index (BMI) and fasting insulin (FI) information available across that time period. FI levels were measured at 9, 15, 18, and 24 years while BMI was measured at 1, 2, 3, 4, 7, 9, 10, 11, 12, 15, 18, and 24 years. A total of 5,790 participants (54.1% female) had sufficient FL level data and 10,463 (51.0% female) had sufficient BMI data. Five distinct trajectories for BMI and three distinct trajectories for FI levels were found, which were evident by mid-childhood. Puberty-onset, major increases in BMI were associated with depression (adjusted OR = 4.46, 95% CI 2.38 to 9.87) but not psychosis (adjusted OR = 1.98, 95% CI 0.56 to 7.79). The trajectory of persistently high Fl levels was associated with a psychosis at-risk mental stated (adjusted OR = 5.01, 95% CI 1.76 to 13.19) and psychotic disorder (adjusted OR = 3.22, 95% CI 1.11 to 9.90) but not depression (adjusted OR = 1.38, 95% CI 0.75 to 2.54). Overall, this study suggests that cardiometabolic comorbidities of psychosis and depression have distinct, early-life origins. Altered insulin sensitivity may be a risk factor for psychosis while major increases in BMI may be a risk factor for depression later in life. This highlights the importance of comprehensive care among individuals with these co-occurring conditions, along with monitoring of potential psychiatric symptoms over time.
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