Abstract
Peripheral inflammation is frequent in schizophrenia and could play a role in the pathophysiology, prognosis, and persistence of psychotic symptomatology under treatment. We seek to determine the relationship between peripheral inflammation and brain SPECT perfusion in stabilized antipsychotic-treated outpatients with schizophrenia, and to determine whether such perfusion changes are correlated with persistent symptoms. Highly sensitive C-reactive protein blood level (hs-CRP) and brain SPECT perfusion were assessed in 137 stabilized outpatients with schizophrenia. Whole-brain voxel-based associations were searched with SPM between SPECT perfusion and hs-CRP (correlation analysis to quantitative levels and between-group analysis according to a threshold of 3mg/L). The identified clusters were secondarily correlated with clinical symptoms. After adjustment for age, sex, educational level, illness duration, antidepressant use, chlorpromazine equivalent dose, tobacco smoking and obesity, a negative correlation was found between hs-CRP level and the perfusion of 4 brain areas: the right inferior frontal gyrus, the right middle/superior temporal gyrus, the left superior parietal lobe, and the right postcentral/transverse temporal gyrus (p-voxel < 0.001, k > 80, uncorrected). Increased perfusion of the left amygdala was found in patients with hs-CRP ≥ 3mg/L compared to those with hs-CRP levels < 3mg/L. A negative correlation was found between perfusion of the right inferior frontal gyrus and the persistence of positive, negative, and excitement symptoms under antipsychotic treatment. In stabilized patients with schizophrenia, peripheral inflammation is associated with brain perfusion changes that are correlated with the persistence of psychotic symptomatology.
Highlights
Elucidating the underlying pathophysiology of schizophrenia may aid in better selection and development of treatments
In stabilized patients with schizophrenia, peripheral inflammation is associated with brain perfusion changes that are correlated with the persistence of psychotic symptomatology
A negative correlation was found between perfusion of the right inferior frontal gyrus and persistence of psychotic symptoms under antipsychotic treatment, of positive, negative and excitement symptoms
Summary
Elucidating the underlying pathophysiology of schizophrenia may aid in better selection and development of treatments. Current biological hypotheses on persistent psychotic symptoms under treatment focus on differences in the functioning of dopaminergic pathways or changes in glutamate or other neurotransmitter pathways. These views are not mutually exclusive, with several pathways converging and possibly contributing to the neurobiology of persistence of psychotic symptoms under treatment. In addition to these possible explanations, we have more than two decades of data highlighting the role of immune-inflammatory processes in schizophrenia. Schizophrenia patients have multiple sources of inflammation including Toxoplasma infection and overweight[5]. We hypothesized that these functional changes would be an indirect marker of persistent psychotic symptoms under antipsychotic treatment
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