Cognitive Impairment in Schizophrenia: Interplay of BDNF and Childhood Trauma? A Review of Literature

Abstract

Cognitive impairment is a core feature of schizophrenia. These deficits can also serve as an endophenotype for the illness in genetic studies. There is evidence that suggests that cognition can be considered a reasonable target for intervention in both schizophrenia and bipolar disorder. One of the most studied genetic phenotypes for psychosis is brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms. BDNF has an established role in neuronal development and cell survival in response to stress and is abnormally expressed in schizophrenia. Studies have shown that childhood trauma is associated with poor prognosis of schizophrenic patients. BDNF-Val66Met polymorphism has been shown to moderate the impact of childhood adversity on later expression of affective symptoms, suggesting the possibility of gene environment interactions. Considering the recent advances of neuroscience an up to date review of relevant literature is warranted in this field. This article reviews the current literature available regarding associations between the Val66Met polymorphism, childhood trauma and cognitive dysfunction in schizophrenia.

Peripheral inflammatory and neurotrophic biomarkers of cognitive impairment in schizophrenia: a meta-analysis

“…The fact that cognitive impairment is evident at first-episode schizophrenia and in individuals who have a genetic or clinical high-risk for developing schizophrenia further supports this notion (Mesholam-Gately et al ., 2009; Agnew-Blais and Seidman, 2013; De Herdt et al ., 2013; Bora et al ., 2014; Bora and Pantelis, 2015). However, other factors such as metabolic syndrome, alcohol use, chronic stress and antipsychotics can also contribute to cognitive impairment in schizophrenia (Potvin et al ., 2008; Thoma and Daum, 2013; Sahu et al ., 2016; Bora et al ., 2017 b ; Omachi and Sumiyoshi, 2018).…”

Evidence that polygenic risk for psychotic disorder is expressed in the domain of neurodevelopment, emotion regulation and attribution of salience

“…The premorbid cognitive alterations in schizophrenia are one of the core findings supporting the neurodevelopmental hypothesis (Jones et al 1994). There was evidence for an association between IQ and PRS, however it may be hypothesized that environmental exposures such as childhood trauma, that have been shown to also impact cognitive development (Majer et al 2010; Gould et al 2012; Maguire et al 2015; Philip et al 2016) may also play a causal role in the development of cognitive alterations in psychosis (Lysaker et al 2001; Aas et al 2012; Sahu et al 2016; Van Os et al 2017). In addition, genetic variation and epistasis not included in the PRS may contribute to cognitive alterations as well.…”

Childhood Trauma in Schizophrenia: Current Findings and Research Perspectives

“…In patients with schizophrenia and affective disorders, an interaction between a variant in the serotonin transporter gene 5-HTTLPR and childhood trauma was observed in the California Verbal Learning Test (Aas et al, 2012a). A variant of BDNF Val66Met polymorphism was shown to moderate the impact of childhood adversity on later expression of affective symptoms in schizophrenia patients (Sahu et al, 2016). In 249 patients with schizophrenia spectrum disorder, carriers of the met allele of the BDNF gene exposed to high levels of childhood physical and emotional abuse demonstrated poorer cognitive functioning than monozygotic valine carriers.…”