Gabriella Riley1, Mary Perrin1, Leila M Vaez-Azizi1, Eugene Ruby2, Raymond R Goetz3, Roberta Dracxler4, Julie Walsh-Messinger5, David L Keefe6, Peter F Buckley7, Philip R Szeszko8, Dolores Malaspina9. 1. Department of Psychiatry, New York University, 1 Park Avenue, 8th Floor Room 222, New York, NY 10016, USA. 2. Department of Psychology, Cognitive Neuroscience, University of California, Los Angeles, USA. 3. New York State Psychiatric Institute at Columbia University, Columbia University Department of Psychiatry, 1051 Riverside Drive, New York, NY 10032, USA. 4. Department of Psychiatry, New York University, 1 Park Avenue, 8th Floor Room 222, New York, NY 10016, USA; Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY 10016, USA. 5. Department of Psychology, University of Dayton, Dayton, OH, USA; Department of Psychiatry, Wright State University Boonshoft School of Medicine, Dayton, OH, USA. 6. Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY 10016, USA. 7. Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA. 8. James J. Peters VA Medical Center, Bronx, NY, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 9. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: dolores.malaspina@mssm.edu.
Abstract
BACKGROUND: Childhood trauma is emerging as a risk factor for schizophrenia, but its mechanism with respect to etiology is unknown. One possible pathway is through leucocyte telomere length (LTL) shortening, a measure of cellular aging associated with trauma. This study examined early trauma and LTL shortening in schizophrenia and considered sex effects. METHODS: The early trauma inventory (ETI) was administered to 48 adults with DSM-5 schizophrenia and 18 comparison participants. LTL was measured using qPCR. OUTCOMES: Cases had significantly more global trauma (F=4.10, p<0.01) and traumatic events (F=11.23, p<0.001), but case and control groups had similar LTL (1.91±0.74 and 1.83±0.62: p=0.68). The association of early trauma and LTL differed by sex in cases and controls (Fisher's R: Z<0.05). Significant negative associations were shown in male cases and, conversely, in female controls. For example, physical punishment was associated LTL shortening in males' cases (r=-0.429, p<01). Only female controls showed significant telomere shortening in association with early trauma. INTERPRETATION: This data confirms the substantial excess of early trauma among schizophrenia cases. There were significant sex-differences in the relationship of the trauma to LTL, with only male cases showing the expected shortening. There were converse sex effects in the control group. Mean LTL was notably similar in cases and controls, despite the trauma-related shortening in male cases, cigarette smoking, older age and chronic illness of the cases. Factors may lengthen LTL in some schizophrenia cases. The converse sex differences in the cases are consistent with findings defective sexual differentiation in schizophrenia, consistent with other findings in the field.
BACKGROUND: Childhood trauma is emerging as a risk factor for schizophrenia, but its mechanism with respect to etiology is unknown. One possible pathway is through leucocyte telomere length (LTL) shortening, a measure of cellular aging associated with trauma. This study examined early trauma and LTL shortening in schizophrenia and considered sex effects. METHODS: The early trauma inventory (ETI) was administered to 48 adults with DSM-5 schizophrenia and 18 comparison participants. LTL was measured using qPCR. OUTCOMES: Cases had significantly more global trauma (F=4.10, p<0.01) and traumatic events (F=11.23, p<0.001), but case and control groups had similar LTL (1.91±0.74 and 1.83±0.62: p=0.68). The association of early trauma and LTL differed by sex in cases and controls (Fisher's R: Z<0.05). Significant negative associations were shown in male cases and, conversely, in female controls. For example, physical punishment was associated LTL shortening in males' cases (r=-0.429, p<01). Only female controls showed significant telomere shortening in association with early trauma. INTERPRETATION: This data confirms the substantial excess of early trauma among schizophrenia cases. There were significant sex-differences in the relationship of the trauma to LTL, with only male cases showing the expected shortening. There were converse sex effects in the control group. Mean LTL was notably similar in cases and controls, despite the trauma-related shortening in male cases, cigarette smoking, older age and chronic illness of the cases. Factors may lengthen LTL in some schizophrenia cases. The converse sex differences in the cases are consistent with findings defective sexual differentiation in schizophrenia, consistent with other findings in the field.
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