Association between a longer duration of illness, age and lower frontal lobe grey matter volume in schizophrenia

The frontal lobe has an extended maturation period and may be vulnerable to the long-term effects of schizophrenia. We tested this hypothesis by studying the relationship between duration of illness (DoI), grey matter (GM) and cerebro-spinal fluid (CSF) volume across the whole brain. Sixty-four patients with schizophrenia and 25 healthy controls underwent structural MRI scanning and neuropsychological assessment. We performed regression analyses in patients to examine the relationship between DoI and GM and CSF volumes across the whole brain, and correlations in controls between age and GM or CSF volume of the regions where GM or CSF volumes were associated with DoI in patients. Correlations were also performed between GM volume in the regions associated with DoI and neuropsychological performance. A longer DoI was associated with lower GM volume in the left dorsomedial prefrontal cortex (PFC), right middle frontal cortex, left fusiform gyrus (FG) and left cerebellum (lobule III). Additionally, age was inversely associated with GM volume in the left dorsomedial PFC in patients, and in the left FG and CSF excess near the left cerebellum in healthy controls. Greater GM volume in the left dorsomedial PFC was associated with better working memory, attention and psychomotor speed in patients. Our findings suggest that the right middle frontal cortex is particularly vulnerable to the long-term effect of schizophrenia illness whereas the dorsomedial PFC, FG and cerebellum are affected by both a long DoI and aging. The effect of illness chronicity on GM volume in the left dorsomedial PFC may be extended to brain structure-neuropsychological function relationships.