Brain derived neurotropic factor (BDNF) is associated with childhood abuse but not cognitive domains in first episode psychosis

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Abstract

Background

The Brain-derived Neurotrophic Factor (BDNF) modulates cognitive processes and is associated with increased risk of schizophrenia. Childhood trauma (CT) is frequent in patients with psychosis and severely affects course and outcome.

Aims

We investigated the hypothesis that BDNF is associated with both CT and cognitive deficits in a sample of first-episode psychosis (FEP) cases and unaffected controls.

Method

Participants with FEP and healthy controls were recruited between August 2008 and July 2011 from South London, UK. Childhood traumatic events were detected using the Childhood Experience of Care and Abuse Questionnaire (CECA-Q). Neuropsychological data were also collected. BDNF plasma levels were measured from fasting blood samples.

Results

Data were available on 87 FEP patients and 152 controls. Our results showed a significant effect of separation (F = 5.5; df = 1,115; p = .02), physical (F = 4.7; df = 1, 118; p = .03) and sexual abuse (F = 5.4; df = 1,117; p = .02) on BDNF levels with lower levels among those who experienced the traumatic event compared to those who did not. Physical abuse predicted lower plasma levels of BDNF (β =  .30; p = .03) whereas sexual and/or physical abuse showed a trend (β =  .26; p = .06) in FEP patients but not in unaffected controls. No association between BDNF plasma levels and cognitive functions was found among patients with FEP and controls.

Conclusion

Our findings suggest the possible involvement of BDNF in the onset of first-episode psychosis in individuals exposed to early trauma and propose BDNF as a potential clinical biomarker to detect the detrimental effects of CT on human brain plasticity.

Introduction

General intellectual impairment is evident across the psychosis spectrum (Bora et al., 2009) and in particular verbal memory, processing speed and IQ have been found to be severely compromised in patients with first-episode psychosis (FEP) (Mesholam-Gately et al., 2009, O'Connor et al., 2012). The Brain-Derived Neurotrophic Factor (BDNF) is considered to modulate cognitive processes (Egan et al., 2003) and BDNF serum levels have been associated with increased risk of schizophrenia (Gratacos et al., 2007). Indeed, in FEP patients' plasma BDNF was found to be associated with poorer performance on cognitive tests (Ruiz de Azua et al., 2013).

Childhood trauma (CT) is prevalent in patients with psychosis and severely affects course and outcome (Schäfer and Fisher, 2011, Várese et al., 2012, Trotta et al., 2013, van Winkel et al., 2013). Patients with FEP who have experienced CT present with worse cognitive performances compared with patients who did not have such early adverse experiences (Aas et al., 2011, Aas et al., 2012a, Aas et al., 2012b). These cognitive deficits may be associated with abnormalities in hippocampal (Mondelli et al., 2011) and amygdala volume (Aas et al., 2012a). Healthy individuals who are Met carriers for the BDNF Val/Met polymorphism and have been exposed to early life stress show smaller amygdala and hippocampal volume associated with a decline in working memory (Gatt et al., 2009). Similarly, in a study involving patients with psychosis, BDNF Met carriers exposed to severe childhood sexual abuse showed reduced right hippocampal volume, larger right and left lateral ventricles and more profound cognitive impairments (specifically executive function/verbal fluency, working memory and verbal abilities (Aas et al., 2013).

There is increasing interest regarding the role of BDNF (Buckley et al., 2007) in the onset of psychosis in patients who have experienced CT in association with cognitive deficits. Ognibene et al. (2008) have demonstrated that early maternal separation had long-term effects on brain plasticity, with a reduction of BDNF in prefrontal cortex and striatum of mice. In addition, Kauer-Sant'Anna et al. (2007) found lower serum BDNF levels in 163 subjects with bipolar disorder and a history of trauma when compared to subjects without such past experiences. However, this association has not been explored specifically in individuals with FEP looking at a range of different traumatic experiences with a case-control design. Therefore, we sought to investigate the hypothesis that BDNF is associated with both CT and cognitive deficits in a study of patients with FEP and unaffected controls recruited from the same geographical location.

Section snippets

Design

This was a case-control study of FEP patients and unaffected controls, conducted in the South London and Maudsley (SLaM) and Oxleas and Sussex Partnership NHS Trusts. The study was approved by the Ethics Committees of these Trusts.

Participants

Between August 2008 and July 2011, patients presenting for the first time to psychiatric services with a functional psychotic illness (ICD-10: F20-29, F30-34 excluding coding F1x.0 for acute intoxication; WHO, 1992), psychotic symptoms lasting for at least 7 days and

Baseline data

A total of 87 patients (57 males, 65.5%) and 152 controls (74 males, 48.6%) were assessed. For demographic characteristcs and main outcome measures of the sample see Table 1. At baseline, 22 patients were drug naïve while 19 were taking risperidone, 31 olanzapine, 10 Aripirazole, 3 Quetiapine, 1 Haloperidol and 1 Trifluoperazine. Average duration of treatment was 10.7 days ± 6.5 with a daily dose of chlopromazine equivalent equal to 196.45 ± 117.39; and a total load of chlorpromazine equivalent of

Discussion

This is the first case-control study that reports an association of physical abuse with BDNF plasma levels in patients with FEP. Our findings confirmed previous studies that looked at the association between childhood trauma (CT), life stressors and BDNF expression in a sample of patients with FEP (Mondelli et al., 2011). The authors reported that a combination of CT and life stressors predicted lower BDNF mRNA expression indicating a pathophysiological pathway of BDNF decrement. This seems to

Role of funding source

This article has been supported with funding from a Young Investigator Award 2009 from NARSAD to Dr. Stefania Bonaccorso. Dr Helen L. Fisher is supported by a UK Medical Research Council Population Health Scientist Award (G1002366). This work was also supported by a grant from the National Institute of Health Research (NIHR) (grant number: RP-PG-0606-1049) and by the National Institute of Health Research Biomedical Research Centre at the South London Foundation Trust and King's College London.

Contributors

S.B. designed the study, wrote the protocol and completed part of the statistical analysis. C.T. and S.B. managed the literature searches and wrote the first draft of the manuscript. D.S. and S.V. undertook the statistical analysis. R.M.M., A.D., H.L.F., C.M., P.M. and C.P. supervised the whole process. All the authors contributed to and have approved the final manuscript.

Conflict of interest

R.M.M. has received honoraria for lectures from Janssen, AstraZeneca, Lilly, Novartis and Bristol-Myers Squibb.

Acknowledgements

The authors gratefully acknowledge the help of the Genetic & Psychosis and Physical Health & Substance Use in First Episode Psychosis study teams and participants, South London & Maudsley Mental Health NHS Trust, the Institute of Psychiatry, King's College London and the National Institute for Health Research Biomedical Research Centre.

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