BACKGROUND: Schizophrenia is associated with elevated levels of circulating C-reactive protein (CRP) and other inflammatory markers, but it is unclear whether these associations extend to psychotic symptoms occurring in adolescence in the general population. A symptom-based approach may provide important clues for apparent trans-diagnostic effect of inflammation, which is also associated with depression and other psychiatric disorders. METHODS: Based on data from 2421 participants from the Avon Longitudinal Study of Parents and Children birth cohort, we examined associations of serum CRP levels assessed around age 16 with ten positive and ten negative symptoms of psychosis assessed using questionnaires around age 17, using both individual symptoms and symptom dimension scores as outcomes. Regression models were adjusted for sex, body mass index, depressive symptoms, substance use, and other potential confounders. RESULTS: Most prevalent positive symptoms were paranoid ideation (4.8%), visual (4.3%) and auditory (3.5%) hallucinations. Negative symptoms were more strongly correlated with concurrent depressive symptoms (r=0.51; P < 0.001) than positive symptoms (rpb=0.19; P < 0.001). The associations of CRP with positive and negative symptom dimension scores were similar. At individual symptom level, after adjusting for potential confounders including depressive symptoms, CRP was associated with auditory hallucinations (adjusted OR = 2.22; 95% CI, 1.04-4.76) and anhedonia (adjusted OR = 1.13; 95% CI, 1.02-1.26). CONCLUSIONS: Inflammation is associated with sub-clinical psychotic symptoms in young people in general population. Association of CRP with symptoms commonly shared between mood and psychotic disorders, such as auditory hallucinations and anhedonia, could be one explanation for the apparent trans-diagnostic effect of inflammation.

Cambridgeshire and Peterborough NHS Foundation Trust Elizabeth House Fulbourn Hospital Fulbourn Cambridge CB21 5EF United Kingdom

Centre for Academic Mental Health Department of Population Health Sciences Bristol Medical School University of Bristol Oakfield House Oakfield Grove Bristol BS8 2BN United Kingdom

Department for Symptom Research University of Texas MD Anderson Cancer Center Laboratory of Neuroimmunology Unit 1055 Office Z8 5042 6565 MD Anderson Boulevard Houston TX 77030 USA

Department of Kinanthropology Charles University José Martího 31 Prague 165 52 Czech Republic

Department of Psychiatry University of Cambridge Herchel Smith Building Forvie Site Cambridge Biomedical Campus Cambridge CB2 0SZ United Kingdom

Division of Psychiatry University College London Maple House 149 Tottenham Court Road London W1T 7NF United Kingdom

Institute of Psychological Medicine and Clinical Neurosciences Cardiff University Cardiff CF10 3AT United Kingdom

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