Guimarães LR, Jacka FN, Gama CS, Berk M, Leitão-Azevedo CL, Belmonte de Abreu MG, Lobato MI, Andreazza AC, Ceresér KM, Kapczinski F, Belmonte-de-Abreu P.
Serum levels of brain-derived neurotrophic factor in schizophrenia on a hypocaloric diet.
Prog Neuropsychopharmacol Biol Psychiatry. 2008 Jun 10. [Epub ahead of print]
PMID: 18582525
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 [HD]. ... The blood sample was obtained a minimum of one month after the exposure to dietary intervention. [The use of serum levels rather than data in specific brain regions is a significant design limitation, due to BDNF's peripheral functions and the fact that BDNF does not cross the intact blood-brain barrier in vivo -- of course, they're not going to autopsy these people, but eg a CSF study would probably be more informative -MR].
Serum BDNF levels were significantly higher in patients on the HD ([1.04 (0.74-2.45) vs 0.86 (0.61-1.14)] p = 0.023)...
1. 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). ...
Several lines of evidence also suggest that BDNF contributes to food intake, metabolism and the control of body weight ([Lebrun et al., 2006] and [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] and [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) [More on BDNF and CR in a previous post -MR]. ...
HD prescription consisted of a caloric restricted diet, a reduction in saturated fat and sugar intake and an increase in fruit and vegetables consumption. [This multi-variable change of course makes it impossible to distinguish any specific effect of Calories vs fat, sugar, or fruit & veg -- but the existing data on CR and BDNF are compelling -MR]. For the females, the caloric intake was between 1600 and 2000 cal/day and for males between 2000 and 2300 cal/day. [Lots of people will think that this is just a normal diet, and will cite standard health websites & gov't authorities; this is largely the result of underreporting. This would represent a nontrivial reduction in energy intake even in many normal-weight individuals, let alone for an overweight cohort; moreover, see below for the acuity of response and lack of adjusted correlation with BMI. Still, I'd obviously like a study in fairly serious human CR -MR] ...
3. Results
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). [This last is interesting, suggesting that the observed CR effect was due to acute energy restriction per se -MR]. There was a positive statistically significant association between BMI and BDNF levels (r = 0.311; p = 0.016) and a correlation trend between daily antipsychotic dose ... However, after multiple linear regression analysis, BMI did not remain associated to serum BDNF levels (p = 0.118). The variables that remained associated to serum BDNF levels were daily antipsychotic dose ... and diet prescription (p = 0.009) (Table 2). Diet was shown as the variable with the highest Beta explanatory power (0.343). [Interestingly, in fact, the control-diet patients, although overweight, were actually slimmer than the treated ones: BMI mean (SD) 29.2 (3.8) vs 26.3 (4.8), P≤ 0.015 -MR]. ... Other authors found this correlation in patients with eating disorders (Nakazato et al., 2003), not undertaken a HD prescription and, possible confounding variables with BDNF levels as the outcome variable were not assessed. ...
Our findings suggest that a calorie-reduced diet that included beneficial changes in types of food consumed as well as quantity may modify important markers of brain plasticity. These results may have additional relevance for psychiatric illnesses other than SZ as BDNF is clearly implicated in the pathophysiology of MDD [major depression] and BD [bipolar disorder] ([Shimizu et al., 2003] and [Palomino et al., 2006]) in addition to SZ...
Credit to Dr. Al Pater on the CR list for the find.
Edited by Michael, 29 September 2008 - 09:36 PM.
