Abstract
BackgroundSchizophrenia 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. MethodsBased 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. ResultsMost 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). ConclusionsInflammation 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.
Highlights
We present a longitudinal study of serum C-reactive protein (CRP) concentration assessed around age years and subsequent self-reported positive and negative symptoms of psychosis assessed around age years in the Avon Lon gitudinal Study of Parents and Children (ALSPAC), a general populationrepresentative birth cohort from the United Kingdom
Evidence for association between CRP levels and auditory halluci nations remained after excluding participants who experienced positive symptoms in the context of cannabis/other drug use, illness or sleep; adjusted odds ratio (OR) = 2.49
After excluding participants with CRP>10 mg/L at baseline, the adjusted OR for anhedonia per Standard Deviation (SD) increase in CRP remained similar to the primary results, but the 95% confidence intervals (CI) widened and included the null; adjusted OR = 1.21
Summary
Low-grade systemic inflammation as reflected by increased concen trations of acute phase proteins, such as C-reactive protein (CRP), and inflammatory cytokines, such as interleukin 6 (IL-6), in peripheral blood has been implicated in pathogenesis of a number of psychiatric disorders including schizophrenia and related psychoses (Khandaker et al, 2015; Miller et al, 2011), depression (Dantzer et al, 2008; Miller et al, 2009), anxiety (Wohleb et al, 2014), post-traumatic stress disorder (Eraly et al, 2014), autism (Brown et al, 2014), Alzheimer’s disease and other de mentias (Schmidt et al, 2002). Longitudinal studies reporting an association between higher blood IL-6, CRP, erythrocyte sedimentation rate (ESR) in childhood/adolescence and increased risks of psychotic symptoms (Khandaker et al, 2014) or diagnosis of schizophrenia (Kappelmann et al, 2019; Metcalf et al, 2017) subsequently in adulthood indicate that inflammation may play a role in causing psychosis rather than being a consequence of illness. Existing studies have reported an association of CRP with negative symptoms (Boozalis et al, 2017), general psychopathology (Fan et al, 2007) and cognitive dysfunction (Dickerson et al, 2007; Johnsen et al, 2016) in patients with psychosis. To our knowledge no population-based studies have examined the association between CRP and positive and negative symptoms of psychosis in a general population-based sample. We have adjusted for these important confounders, and carried out sensitivity analyses after excluding par ticipants who reported positive symptoms in the context of drugs, physical illness or sleep
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