The Impact of Childhood Trauma on the Association Between Inflammation and Negative Symptoms of Schizophrenia Pubblico

Abstract

Schizophrenia is a severe and multifactorial psychiatric disorder that is characterized by a combination of positive, negative, and cognitive symptoms. Negative symptoms are strongly associated with worse functional outcomes and the immense illness burden. Because inflammatory markers are associated with negative symptoms in schizophrenia, immune system abnormalities may be one mechanism behind these symptoms. In addition to being a risk factor for schizophrenia, childhood trauma has been associated with elevated systemic inflammation in adulthood and worse negative symptoms. Considering past literature has identified a positive association between both inflammation and negative symptoms of schizophrenia as well as childhood trauma and psychopathology severity in schizophrenia populations, we hypothesized that pro-inflammatory cytokines would be positively correlated with negative symptoms as well as childhood trauma prevalence. Additionally, we hypothesized that childhood physical and emotional neglect, rather than the other childhood trauma subtypes, will be positively associated with greater negative symptoms. Fifty individuals from Grady Memorial Hospital’s psychiatric outpatient clinics who met the criteria for schizophrenia or schizoaffective disorder were enrolled in the study. During enrollment, each patient completed behavioral questionnaires, was interviewed for psychiatric/medical history and demographic information, and provided blood for screening labs and assay of inflammatory markers. We found that childhood emotional and physical neglect were positively correlated with the deficits of motivated behavior domain of negative symptoms (AAA: avolition, asociality, anhedonia), as indexed by the Brief Negative Symptom Scale (BNSS). In individuals with high BNSS AAA scores, we identified positive trends for a relationship between TNF-α with childhood trauma overall, as well as emotional abuse and physical neglect. When looking at the subgroup of patients with both high BNSS AAA scores and high inflammation (as indexed by CRP), we found a positive correlation between the pro-inflammatory cytokine IL-6 with the CTQ Physical Neglect subscale. Our findings regarding childhood trauma and negative symptoms align with theoretical pathways that suggest how childhood trauma can lead to negative symptoms later in life. Considering the literature linking inflammation to negative symptoms, childhood trauma may be involved in negative symptoms via disruptions in the inflammatory response.

Table of Contents

Introduction………………………………………………………..……………………………...1

           Schizophrenia……………………………………………..………………………………1

           Inflammation: the Role of Peripheral Cytokines…..……..….……………………………2

           Inflammation and Schizophrenia………………….………………………………………4

           Childhood Trauma……………………………………..….………………………………7           

          Childhood Trauma and Psychiatric Illness…………..……………………………………9

            Childhood Trauma and Inflammation in Schizophrenia…………..……………………..10

           Childhood Trauma and Negative Symptoms in Schizophrenia……...…………………..12

           Purpose and Hypotheses of the Present Study……………….…………………………..13

Methods…...………………………………………………………..…………………………….15

           Subjects……..……………………………………………..……………………………..15

            Behavioral and Psychiatric Screenings...………….……………………………………..15

            Blood Draw and Laboratory Samples….………….……………………………………..17

            Statistical Analyses………………………………………………………………………17

Results..…...………………………………………………………..…………………………….19

            Sample Demographic, Behavioral, and Blood Characteristics…………………………..19

           Bivariate Correlations……………….....………….……………………………………..19

Discussion...………………………………………………………..…………………………….22

           Relationship between Inflammation, Childhood Trauma, and Negative Symptoms…….22

           Limitations………….……………….....………….……………………………………..27

          Future Directions..….……………….....………….……………………………………..28

References...………………………………………………………..…………………………….30

Tables and Figures...………...……………………………………..…………………………….45

About this Honors Thesis

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School	Emory College
Department	Neuroscience and Behavioral Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Neuroscience Health Sciences, Immunology Psychology, Psychobiology
Parola chiave	Childhood Trauma Motivational Deficits Negative Symptoms Schizophrenia Inflammation
Committee Chair / Thesis Advisor	Goldsmith, David, Emory University
Committee Members	Crutcher, Michael, Emory University Walker, Elaine, Emory University

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