Serum levels of brain-derived neurotrophic factor in schizophrenia on a hypocaloric diet

https://doi.org/10.1016/j.pnpbp.2008.06.004Get rights and content

Abstract

Dietary factors influence BDNF in animal studies, but there is no comparable data in clinical populations. We examined the effect of a dietary intervention on BDNF serum levels in 67 DSM-IV schizophrenic outpatients (51 males and 16 females). Two groups were assessed in a cross-sectional study: one on a hypocaloric diet (HD) and the other not on a hypocaloric diet. Weight, height and BMI data were collected concurrently with 5-ml blood sampling of each subject. BDNF levels were measured with a sandwich-ELISA. The blood sample was obtained a minimum of one month after the exposure to dietary intervention. Serum BDNF levels were significantly higher in patients on the HD (p = 0.023). Additional research examining the interaction among patterns of nutritional food behavior and underlying physiopathology may result in insights upon which evidence-based decisions regarding dietary interventions can be made in people identified with major psychiatric disorders, such as schizophrenia.

Introduction

The pathophysiology of schizophrenia (SZ) may involve deregulation in synaptic plasticity, with downstream alterations in neurotrophins (Gratacos et al., 2007). Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophin in the central nervous system (CNS) and is regarded as a critically important protein in psychiatric illness (Hashimoto et al., 2004). It promotes neurogenesis, supports the survival of existing neurons by protecting against oxidative stress and plays a central role in synaptic plasticity. Decreased levels of BDNF have been reported in major depression (MDD) (Shimizu et al., 2003), bipolar disorder (BD) and SZ first episode schizophrenia (Palomino et al., 2006), while levels of BDNF are negatively correlated with illness severity in both BD (Cunha et al., 2006) and SZ (Tan et al., 2005). Conversely, increased levels of BDNF have been reported in SZ patients on long-term treatment with antipsychotic medication (Gama et al., 2007).

Recent evidence points to the role of diet in regulating BDNF. Experimental studies in rodents have demonstrated that a high-fat, refined sugar diet, similar in composition to the typical diet of industrialized western nations, significantly reduces BDNF in the hippocampus, with resulting impairments in spatial learning (Molteni et al., 2002). Of additional interest is the fact that reductions in BDNF induced by a high-saturated fat (HF) diet, as well as HF-impaired cognitive function, were subsequently reversed by vitamin E supplementation (Wu et al., 2004a), while dietary omega 3 polyunsaturated fatty acids normalized BDNF levels and counteracted learning disabilities after brain injury (Wu et al., 2004b).

Several lines of evidence also suggest that BDNF contributes to food intake, metabolism and the control of body weight (Lebrun et al., 2006, Zhang et al., 2007). Individuals with schizophrenia are more likely to be obese than unaffected individuals, largely due to the use of antipsychotic medication, which is associated with weight gain, hyperglycemia and dyslipidemia (Leitão-Azevedo et al., 2006). Smoking, poor diet, reduced physical activity and alcohol or drug abuse are also more prevalent in people with schizophrenia, compounding the risk of metabolic problems (Barnett et al., 2007). Thus, dietary interventions that aim to reduce these risks are now commonly prescribed for patients with SZ.

In animal models, environmental interventions, such as diet, housing and social interactions, have been reported to alter the concentration of BDNF (Koizumi et al., 2006, Strasser et al., 2006), while dietary restriction was associated with behavioral changes and significantly increased 5-HT in the hippocampus of heterozygous BDNF mice (Strasser et al., 2006).

Given the clear role of diet in the modulation of BDNF in animal studies, and the evidence indicating that BDNF is involved in modifying food intake and metabolism, in a cross-sectional study we assessed serum levels of BDNF in SZ patients undertaking a hypocaloric dietary intervention compared to a group receiving treatment as usual.

Section snippets

Methods

The study sample comprised of 67 Caucasian outpatients (51 males and 16 females), mean age 35.5 ± 10.7 years, currently participating in the Schizophrenia Program of a major teaching and public hospital in Porto Alegre, Brazil (Hospital de Clínicas de Porto Alegre — HCPA). All participants had a DSM-IV diagnosis of schizophrenia by the OPCRIT system (Craddock et al., 1996, Azevedo et al., 1999) and a Clinical Global Impression (CGI) (Guy, 1976) score ≤ 3 as assessed by a trained psychiatrist. None

Results

The subjects' clinical characteristics at time of blood assessment are summarized in Table 1. Our study shows that there was a statistically significant difference between BDNF levels in patients from groups HD and ND, with higher levels in the HD group (p = 0.023) (Table 1). Serum BDNF levels were not correlated to age (r = 0.091; p = 0.464), illness duration (r = 0.057; p = 0.662) and diet duration (r = 0.326); p = 0.150). There was a positive statistically significant association between BMI and BDNF

Discussion

To our knowledge, this is the first report of increased BDNF serum levels in patients with SZ who were prescribed a HD. Higher BDNF levels were found in patients with higher antipsychotic daily doses, which is in line with both the known property of atypicals to increase BDNF, and the literature demonstrating higher BDNF levels in chronically medicated SZ patients (Gama et al., 2007).

We found a positive correlation between BMI and BDNF serum levels. However, after multiple linear regression

Conclusion

This study suggests that diet may influence BDNF levels in SZ and, thus, may have the potential to influence the course and clinical outcomes of psychiatric illness. Additional research examining the interaction among patterns of nutritional food behavior with underlying physiopathology may result in insights upon which evidence-based decisions regarding dietary interventions can be made in people identified with major psychiatric disorders, such as SZ.

Acknowledgements

Clarissa Severino Gama is funded by CNPq (PDE #200310/2007-0), Brazil; and Endeavour Awards Programme (#539/2008), Australia.

References (28)

Cited by (31)

  • Implication of saturated fats in the aetiology of childhood attention deficit/hyperactivity disorder – A narrative review

    2022, Clinical Nutrition ESPEN
    Citation Excerpt :

    However, some dietary intervention studies provided preliminary evidence of the relationship between SFs intake and circulating BDNF concentrations. These studies investigated the effect of a hypocaloric diet, characterised by a decrease in SFs intake, on peripheral BDNF concentrations [79,80]. One study investigated the effect of a reduced-calorie diet (SFs <10% energy intake) on serum BDNF concentration over a period of 3 months in 17 obese subjects [79].

  • Towards an understanding of the physical activity-BDNF-cognition triumvirate: A review of associations and dosage

    2020, Ageing Research Reviews
    Citation Excerpt :

    Alongside physical activity, which is discussed in detail in the following sections, BDNF is modulated by several factors, including acute responses to passive environmental heat exposure (Kojima et al., 2018), intravenous tetrahydrocannabinol administration (D’Souza et al., 2009), hypoxic stress (Helan et al., 2014), electroconvulsive therapy (Salehi et al., 2016) and long-term factors such as exposure to sunlight and time of year (Molendijk, Haffmans, et al., 2012a,b), environmental enrichment (Falkenberg et al., 1992; Ickes et al., 2000) and schizophrenia (Palomino et al., 2006). Caloric restriction significantly increases serum BDNF after one month (Guimaraes et al., 2008), with a 25 % caloric reduction associated with an increase of serum BDNF from 3.97 ± 0.87 to 6.75 ± 1.62 ng/ml after three months in a sample (n = 17) aged 24–48 years (Araya et al., 2008). Fasting can be distinguished from caloric restriction in that its health benefits in humans and animals appear to arise from the duration between meals, rather than the total calories consumed (Paoli et al., 2019).

  • Refining and integrating schizophrenia pathophysiology - Relevance of the allostatic load concept

    2014, Neuroscience and Biobehavioral Reviews
    Citation Excerpt :

    Emerging evidence indicates that BDNF plasma level and its polymorphisms may predict weight gain associated with antipsychotic treatment (Lane et al., 2006; Tsai et al., 2011; Zai et al., 2012; Zhang et al., 2007, 2008). In addition, it has been found that life style modification to reduce body weight increases BDNF level in non-diabetic schizophrenia subjects (Guimaraes et al., 2008; Kuo et al., 2013). BDNF level and its polymorphisms are also known to influence treatment response and adverse effects associated with antipsychotics.

View all citing articles on Scopus
View full text