title: Pathways Associating Childhood Trauma to the Neurobiology of Schizophrenia.
abstract: While researchers have for decades considered the role of social factors, endocrinology, neural function, hippocampal integrity, and cognition in the development of schizophrenia, there has been a relative paucity of studies considering the participation of the stress cascade in the interplay of these elements. As described in this review, stressful exposures and stress sensitivity may plausibly be argued to play a role in the etiology, neurobiology, and course of schizophrenia and related psychotic disorders. Notably, research conducted over the last decade has made it increasingly clear that childhood traumatic experiences represent a prominent risk factor for the development of psychotic disorders, including schizophrenia. Accumulating evidence suggests that this relationship is mediated by the development of a neuropathological stress response, involving HPA axis dysregulation, aberrant functioning of different neurotransmitter systems, hippocampal damage, and memory deficits. However, it remains difficult to identify exact causal pathways linking early trauma to schizophrenia, including to the individual symptoms associated with the disorder. In addition to the strong association among early trauma, stress sensitization, and positive symptoms in schizophrenia, there is also evidence indicating that the negative and cognitive symptoms are related to these factors. However, the emergence of these symptoms may lie on a distinct and non-interacting pathway in relation to the development of the positive symptoms. The natural increases in stress sensitivity and HPA axis activity during adolescence may act on already maladaptive stress circuitry resulting from early trauma and/or a genetic predisposition to produce full blown stress sensitization and cause epigenetic effects, such as the altered methylation of different genes, that lead to schizophrenia or other psychiatric illnesses.
authors.affiliation: Institute for Social and Psychiatric Initiatives - Research, Education, and Services (InSPIRES), Department of Psychiatry, New York University School of Medicine, 462 First Avenue, OBV A-Building, Rm 857, New York, NY 10016, USA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Ruby
authors.affiliation: New York State Psychiatric Institute at Columbia University, 1051 Riverside Drive, New York, NY 10032, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Polito
authors.affiliation: Creedmoor Psychiatric Center, New York State Office of Mental Health, 79-25 Winchester Boulevard, Queens Village, New York, 11427, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: McMahon
authors.forename: Marisa
authors.initials: M
authors.lastname: Gorovitz
authors.forename: Cheryl
authors.initials: C
authors.lastname: Corcoran
authors.forename: Dolores
authors.initials: D
authors.lastname: Malaspina
keywords: Childhood Trauma; Childhood Traumatic Experiences; Early Trauma; Epidemiology of Schizophrenia; Etiology of Schizophrenia; Neurobiology of Schizophrenia; Schizophrenia; Stress Sensitivity; Stress Sensitization