Metabolic trajectories in childhood and adolescence: Effects on risk for schizophrenia

Abstract

Abnormal glucose and lipid metabolism is common in antipsychotic-naive first-episode patients with schizophrenia, but it is unclear whether these changes can already be seen in premorbid or prodromal period, before the first psychotic episode. We examined insulin, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride trajectories in children and adolescents (9-18 years old), who were later diagnosed with schizophrenia, any non-affective psychosis (NAP) or affective disorder (AD). The study population consisted of a general population-based cohort "The Cardiovascular Risk in Young Finns Study", started in 1980 (n = 3596). Psychiatric diagnoses were derived from the Health Care Register up to the year 2018. Multivariate statistical analysis indicated no significant differences in insulin or lipid levels in children and adolescents who later developed schizophrenia (n = 41) compared to the cohort control group (n = 3202). In addition, no changes in these parameters were seen in the NAP (n = 74) or AD (n = 156) groups compared to the controls, but lower triglyceride levels in childhood/adolescence associated with earlier diagnosis of psychotic disorder in the NAP group. Taken together, our results do not support any gross-level insulin or lipid changes during childhood and adolescence in individuals with later diagnosis of schizophrenia-spectrum disorder. Since changes in glucose and lipid metabolism can be observed in neuroleptic-naive patients with schizophrenia, we hypothesize that the more marked metabolic changes develop during the prodrome closer to the onset of the first psychotic episode. The findings have relevance for studies on developmental hypotheses of schizophrenia.

Fig. 1. Childhood and adolescence lipid and insulin levels in participants who later developed schizophrenia, any non-affective psychosis and controls.

Mean (95% CI) fasting plasma insulin^*, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride* levels in children and adolescents (9–18 years of age) who later developed A schizophrenia^a or B any non-affective psychosis^b and controls. Gray dashed line = individuals who later developed schizophrenia, gray dash-dotted line = individuals who later developed any non-affective psychosis and black solid line = controls with no psychiatric diagnoses during the follow-up 1980–2018. *geometric means. ^aDSM-IV diagnosis 295. ^bDSM-IV diagnoses 295, 297, and 298.