Inflammation, hippocampal volume, and cognition in schizophrenia: results from the Northern Finland Birth Cohort 1966

Increased blood interleukin-6 (IL-6) levels are a replicated abnormality in schizophrenia, and may be associated with smaller hippocampal volumes and greater cognitive impairment. These findings have not been investigated in a population-based birth cohort. The general population Northern Finland Birth Cohort 1966 was followed until age 43. Subjects with schizophrenia were identified through the national Finnish Care Register. Blood IL-6 levels were measured in n = 82 subjects with schizophrenia and n = 5373 controls at age 31. Additionally, 31 patients with schizophrenia and 63 healthy controls underwent brain structural MRI at age 34, and cognitive testing at ages 34 and 43. Patients with schizophrenia had significantly higher median (interquartile range) blood IL-6 levels than controls (5.31, 0.85-17.20, versus 2.42, 0.54-9.36, p = 0.02) after controlling for potential confounding factors. In both schizophrenia and controls, higher blood IL-6 levels were predictors of smaller hippocampal volumes, but not cognitive performance at age 34. We found evidence for increased IL-6 levels in patients with midlife schizophrenia from a population-based birth cohort, and replicated associations between IL-6 levels and hippocampal volumes. Our results complement and extend the previous findings, providing additional evidence that IL-6 may play a role in the pathophysiology of schizophrenia and associated brain alterations.