Longitudinal Trends in Insulin Levels and BMI From Childhood and Their Associations with Risks of Psychosis and Depression in Young Adults

Research output: Contribution to journalArticlepeer-review


  • Benjamin Ian Perry
  • Jan Stochl
  • Stanley Zammit
  • Nick Wareham
  • Claudia Langenberg
  • Eleanor Winpenny
  • David B Dunger
  • Peter Jones
  • Golam M Khandaker

Colleges, School and Institutes

External organisations

  • University of Cambridge
  • Cambridgeshire and Peterborough NHS Foundation Trust


Importance: Cardiometabolic disorders often co-occur with psychosis and depression, contribute to higher mortality rates, and are detectable from the onset of the psychiatric disorders. However, it is unclear how longitudinal trends in cardiometabolic traits from childhood relate to risks of adult psychosis and depression.

Objective: To examine whether specific developmental trajectories of fasting insulin (FI) and body mass index (BMI) from early-childhood were longitudinally associated with adult psychosis and depression.

Design: Cohort study from Avon Longitudinal Study of Parents and Children (ALSPAC) using data from 1-24y.

Setting: Prospective population-representative British birth cohort.

Participants: BMI and FI data obtained from 10,463 and 5,790 participants, respectively, used for growth mixture modelling to delineate developmental trajectories. Associations with psychosis and depression were assessed on 3,804 and 3,795 participants, respectively.

Exposures: FI was measured at 9, 15, 18 and 24y. BMI was measured at 1, 2, 3, 4, 7, 9, 10, 11, 12, 15, 18 and 24y. We included sex, ethnicity, paternal social class, childhood emotional and behavioural problems, and cumulative scores of sleep problems, average calorie intake, physical activity, smoking, alcohol and substance use in childhood/adolescence as potential confounders.

Outcomes: Psychosis risk (definite psychotic experiences, psychotic disorder, at-risk mental state status, and negative symptom score) and depression risk (ICD-10 depressive episode, depression symptom score) assessed at 24y.

Results: From 5,790 participants (45.9% male) for FI, and 10,463 participants (49.0% male) for BMI, we identified three distinct trajectories for FI, and five for BMI, all of which were clearly differentiated by mid-childhood. The persistently high FI trajectory was associated with psychosis at-risk mental state (adjusted OR=5.01; 95% C.I., 1.76-13.19) and psychotic disorder (adjusted OR=3.22; 95% C.I., 1.11-9.90), but not depression. Puberty-onset major BMI increase was associated with depression (adjusted OR=4.46; 95% C.I., 2.38-9.87), but not psychosis.

Conclusions and Relevance: 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. Puberty-onset major BMI increase could be a risk factor/risk indicator for depression. These markers may represent important targets for treatment/prevention of cardiometabolic disorders in psychosis and depression


Original languageEnglish
JournalJAMA psychiatry
Publication statusAccepted/In press - 11 Nov 2020