Association of complement component C4 with conversion to psychosis among adolescents at clinical high risk of psychosis Open Access

Raina, Rutika (Spring 2020)

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Introduction- Schizophrenia is a severe psychiatric disorder, heritable and mechanistically complex in nature. Early genetic associations suggested variation in the Major Histocompatibility Complex (MHC) locus. Recent studies have found evidence to suggest an association between different levels of risk for development of schizophrenia due to copy number variation in C4A and C4B expression (1). The increasing interest for the detection and treatment of schizophrenia has led to focused research on the pre-onset period (prodromal) as the window of opportunity for preventive intervention.

Methods- Seventy-eight individuals from the North American Prodromal Longitudinal Study who met clinically high risk (CHR) criteria were included in the study. Complement component C4 was measured in the saliva at baseline. Structure Interview of Prodromal Symptoms were measured at baseline and follow up data was collected at six, twelve, eighteen and twenty-four months. Association between complement component C4 at baseline and conversion to psychosis at the end of two years was assessed using logistic regression model controlling for age, sex, race and income status.

Results- Cases and controls did not vary on demographics at baseline. Baseline levels of complement component C4 did not predict conversion to psychosis of individuals at CHR for psychosis (OR= 0.96, 95% CI= (0.85, 1.08), p-value= 0.50). The most common positive symptoms were unusual thought content and perceptual abnormalities while the most common negative symptom was occupational functioning. Disorganization symptoms were witnessed less frequently except for trouble with focus and attention while all other general symptoms were witnessed more than 50% except for motor disturbances.

Conclusions- Theses findings suggest that there is no significant association between C4 as a biomarker in the underlying mechanism involved with the risk of converting to schizophrenia among youth at CHR of psychosis. Future studies with larger samples are needed to confirm and extend these results.

Table of Contents

1. Introduction ------------------------------------------------------------------------------------ 1

2. Literature Review ------------------------------------------------------------------------------- 4

2.1 The Immune system --------------------------------------------------------------------------- 4

2.1.1 Overview of the complement system -------------------------------------------------------- 5

2.2 Complement component C4 ------------------------------------------------------------------- 6

2.2.1 Complement C4 and schizophrenia risk ----------------------------------------------------- 7

2.3 Schizophrenia and other psychotic disorders -------------------------------------------------- 9

2.3.1 Schizophrenia as a global health problem -------------------------------------------------- 10

2.3.2 Early detection and intervention in schizophrenia psychosis ------------------------------- 11

2.4 The North American Prodromal Longitudinal Study ------------------------------------------ 12

3. Methods ---------------------------------------------------------------------------------------- 13

3.1 Study Design and Study Population ----------------------------------------------------------- 13

3.2 Saliva Collection and C4 assay----------------------------------------------------------------- 14

3.3 Outcome Assessment --------------------------------------------------------------------------14

3.4 Statistical Analysis ---------------------------------------------------------------------------- 15

4. Results ------------------------------------------------------------------------------------------17

5. Discussion -------------------------------------------------------------------------------------- 20

6. References -------------------------------------------------------------------------------------- 22

7. Tables ------------------------------------------------------------------------------------------- 27

7.1 Table 1 ----------------------------------------------------------------------------------------- 27

7.2 Table 2 ----------------------------------------------------------------------------------------- 28

8 Figures -------------------------------------------------------------------------------------------29

9. Appendices ------------------------------------------------------------------------------------- 65

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