Abstract
Schizophrenia is a severe neuropsychiatric disorder with persistence of symptoms throughout adult life in most of the affected patients. This unfavorable course is associated with multiple episodes and residual symptoms, mainly negative symptoms and cognitive deficits. The neural diathesis-stress model proposes that psychosocial stress acts on a pre-existing vulnerability and thus triggers the symptoms of schizophrenia. Childhood trauma is a severe form of stress that renders individuals more vulnerable to developing schizophrenia; neurobiological effects of such trauma on the endocrine system and epigenetic mechanisms are discussed. Childhood trauma is associated with impaired working memory, executive function, verbal learning, and attention in schizophrenia patients, including those at ultra-high risk to develop psychosis. In these patients, higher levels of childhood trauma were correlated with higher levels of attenuated positive symptoms, general symptoms, and depressive symptoms; lower levels of global functioning; and poorer cognitive performance in visual episodic memory end executive functions. In this review, we discuss effects of specific gene variants that interact with childhood trauma in patients with schizophrenia and describe new findings on the brain structural and functional level. Additive effects between childhood trauma and brain-derived neurotrophic factor methionine carriers on volume loss of the hippocampal subregions cornu ammonis (CA)4/dentate gyrus and CA2/3 have been reported in schizophrenia patients. A functional magnetic resonance imaging study showed that childhood trauma exposure resulted in aberrant function of parietal areas involved in working memory and of visual cortical areas involved in attention. In a theory of mind task reflecting social cognition, childhood trauma was associated with activation of the posterior cingulate gyrus, precuneus, and dorsomedial prefrontal cortex in patients with schizophrenia. In addition, decreased connectivity was shown between the posterior cingulate/precuneus region and the amygdala in patients with high levels of physical neglect and sexual abuse during childhood, suggesting that disturbances in specific brain networks underlie cognitive abilities. Finally, we discuss some of the questionnaires that are commonly used to assess childhood trauma and outline possibilities to use recent biostatistical methods, such as machine learning, to analyze the resulting datasets.
Highlights
Schizophrenia is a severe neuropsychiatric disorder that affects about 1% of the population (Jablensky, 1995)
These deficits may lead to memory decline, social withdrawal, and impaired social and role functioning as measured by the Global Assessment of Functioning (GAF) scale (Green et al, 2015a)
Twin studies found a heritability of about 60–80% for schizophrenia (Sullivan et al, 2003), and new genome-wide association studies (GWASs) revealed a total of 145 genetic risk loci, the single nucleotide polymorphisms (SNPs), each with only a weak effect (Pardinas et al, 2018)
Summary
Schizophrenia is a severe neuropsychiatric disorder that affects about 1% of the population (Jablensky, 1995). The disorder is among the leading cause of years lived with disability worldwide (Whiteford et al, 2013), and, among all mental illnesses, schizophrenia is associated with the highest socioeconomic costs (Gustavsson et al, 2011) This high disorder burden is due to the early onset of schizophrenia in late adolescence and early adulthood and the persistence of symptoms throughout adult life in over 90% of affected patients despite meeting remission criteria (Häfner and an der Heiden, 2007; Schennach et al, 2015). Cognitive deficits as a core feature of the disorder are present in domains such as episodic memory, executive function, social cognition, and attention (Green, 1996; Hoff et al, 2005) These deficits may lead to memory decline, social withdrawal, and impaired social and role functioning as measured by the Global Assessment of Functioning (GAF) scale (Green et al, 2015a). While childhood trauma has been repeatedly shown to negatively impact “recovery” among schizophrenia patients (Alameda et al, 2015, 2017; Trauelsen et al, 2016), some of these findings were only partially replicated (Trotta et al, 2016; Ajnakina et al, 2018), hereby leading to a rather heterogeneous body of evidence and emphasizing the need for further research into the neurobiological underpinnings of this association
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