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Brain-derived neurotrophic factor (BDNF) and set-shifting in currently ill and recovered anorexia nervosa (AN) patients

Published online by Cambridge University Press:  28 August 2008

M. Nakazato*
Affiliation:
Section of Eating Disorders, Institute of Psychiatry, King's CollegeLondon, UK Department of Child Psychiatry, Chiba University Hospital, Chiba, Japan
K. Tchanturia
Affiliation:
Section of Eating Disorders, Institute of Psychiatry, King's CollegeLondon, UK
U. Schmidt
Affiliation:
Section of Eating Disorders, Institute of Psychiatry, King's CollegeLondon, UK
I. C. Campbell
Affiliation:
Section of Eating Disorders, Institute of Psychiatry, King's CollegeLondon, UK
J. Treasure
Affiliation:
Division of Psychological Medicine, Eating Disorders Research Unit, Department of Academic Psychiatry, King's College, Guy's Hospital,London, UK
D. A. Collier
Affiliation:
Division of Psychological Medicine and Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's CollegeLondon, UK
K. Hashimoto
Affiliation:
Division of Clinical Neuroscience, Chiba University Centre for Forensic Mental Health, Chiba, Japan
M. Iyo
Affiliation:
Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan
*
*Address for correspondence: Dr M. Nakazato, Section of Eating Disorders, PO59, Institute of Psychiatry, London SE5 8AF, UK. (Email: michiko.nakazato@nifty.ne.jp)

Abstract

Background

Studies of patients with anorexia nervosa (AN) have shown that they do not perform well in set-shifting tasks but little is known about the neurobiological correlates of this aspect of executive function. The aim of this study was to measure serum brain-derived neurotrophic factor (BDNF) and to establish whether set-shifting difficulties are present in people with current AN and in those recovered from AN, and whether serum BDNF concentrations are correlated with set-shifting ability.

Method

Serum BDNF concentrations were measured in 29 women with current AN (AN group), 18 women who had recovered from AN (ANRec group) and 28 age-matched healthy controls (HC group). Set-shifting was measured using the Wisconsin Card Sorting Test (WCST). Eating-related psychopathology and depressive, anxiety and obsessive–compulsive symptomatology were evaluated using the Eating Disorder Examination Questionnaire (EDEQ), the Hospital Anxiety and Depression Scale (HADS), and the Maudsley Obsessive–Compulsive Inventory (MOCI) respectively.

Results

Serum BDNF concentrations (mean±s.d.) were significantly lower in the AN group (11.7±4.9 ng/ml) compared to the HC group (15.1±5.5 ng/ml, p=0.04) and also compared to the ANRec group (17.6±4.8 ng/ml, p=0.001). The AN group made significantly more errors (total and perseverative) in the WCST relative to the HC group. There was no significant correlation between serum BDNF concentrations and performance on the WCST.

Conclusions

Serum BDNF may be a biological marker for eating-related psychopathology and of recovery in AN. Longitudinal studies are needed to explore possible associations between serum BDNF concentrations, illness and recovery and neuropsychological traits.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2008

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References

APA (2000). Diagnostic and Statistical Manual of Mental Disorders, 4th edn, text revision (DSM-IV-TR). American Psychiatric Association: Washington, DC.Google Scholar
Collier, D, Treasure, J (2004). The etiology of eating disorders. British Journal of Psychiatry 185, 363365.CrossRefGoogle ScholarPubMed
Connan, F, Campbell, I, Katzman, M, Lightman, S, Treasure, J (2003). A neurodevelopmental model for anorexia nervosa. Physiology and Behavior 79, 1324.CrossRefGoogle ScholarPubMed
Dempster, E, Toulopoulou, T, McDonald, C, Bramon, E, Walshe, M, Filbey, F, Wickham, H, Sham, PC, Murray, RM, Collier, DA (2005). Association between BDNF val66 met genotype and episodic memory. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 134, 7375.CrossRefGoogle Scholar
Egan, MF, Kojima, M, Callicott, JH, Goldberg, TE, Kolachana, BS, Bertolino, A, Zaitsev, E, Gold, B, Goldman, D, Dean, M, Lu, B, Weinberger, DR (2003). The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 112, 257269.CrossRefGoogle ScholarPubMed
Fassino, S, Pieró, A, Daga, GA, Leombruni, P, Mortara, P, Rovera, GG (2002). Attentional biases and frontal functioning in anorexia nervosa. International Journal of Eating Disorders 31, 274283.CrossRefGoogle ScholarPubMed
Fairburn, C, Beglin, S (1994). Assessment of eating disorders: interview or self-report questionnaire? International Journal of Eating Disorders 16, 363370.3.0.CO;2-#>CrossRefGoogle ScholarPubMed
Galderisi, S, Mucci, A, Monteleone, P, Sorrentino, D, Piegari, G, Maj, M (2003). Neurocognitive functioning in subjects with eating disorders: the influence of neuroactive steroids. Biological Psychiatry 53, 921927.CrossRefGoogle ScholarPubMed
Gillberg, C, Råstam, M, Gillberg, I (1994 b). Anorexia nervosa: physical health and neurodevelopment at 16 and 21 years. Developmental Medicine and Child Neurology 36, 567575.CrossRefGoogle Scholar
Gillberg, I, Gillberg, C, Råstam, M, Johansson, M (1996). The cognitive profile of anorexia nervosa: a comparative study including a community-based sample. Comprehensive Psychiatry 37, 2330.CrossRefGoogle ScholarPubMed
Gillberg, I, Råstam, M, Gillberg, C (1994 a). Anorexia nervosa outcome: six-year controlled longitudinal study of 51 cases including a population cohort. Journal of the American Academy of Child and Adolescent Psychiatry 33, 729739.CrossRefGoogle ScholarPubMed
Hashimoto, K, Koizum, H, Nakazato, M, Shimizu, E, Iyo, M (2005). Role of brain-derived neurotrophic factor in eating disorders: recent findings and its pathophysiological implications. Progress in Neuro-Psychopharmacology and Biological Psychiatry 29, 499504.CrossRefGoogle ScholarPubMed
Hodgson, R, Rachman, S (1977). Obsessional-compulsive complaints. Behaviour Research and Therapy 15, 389395.CrossRefGoogle ScholarPubMed
Holliday, J, Tchanturia, K, Landau, S, Collier, D, Treasure, J (2005). Is impaired set-shifting an endophenotype of anorexia nervosa? American Journal of Psychiatry 162, 22692275.CrossRefGoogle ScholarPubMed
Kernie, S, Liebl, D, Parada, L (2000). BDNF regulates eating behavior and locomotor activity in mice. EMBO Journal 19, 12901300.CrossRefGoogle ScholarPubMed
Koizumi, H, Hashimoto, K, Itoh, K, Nakazato, M, Shimizu, E, Ohgake, S, Koike, K, Okamura, N, Matsushita, S, Suzuki, K, Murayama, M, Higuchi, S, Iyo, M (2004). Association between the brain-derived neurotrophic factor 196G/A polymorphism and eating disorders. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 127, 125127.CrossRefGoogle Scholar
Koizumi, H, Hashimoto, K, Iyo, M (2006). Dietary restriction changes behaviors in brain-derived neurotrophic factor heterozygous mice: role of serotonergic system. European Journal of Neuroscience 24, 23352344.CrossRefGoogle ScholarPubMed
Lezak, M (1995). Neuropsychological Assessment. Oxford University Press: Oxford.Google Scholar
Lindsay, R, Wiegand, S, Altar, C, Di Stefano, P (1994). Neurotrophic factors: from molecule to man. Trends in Neurosciences 17, 182190.CrossRefGoogle ScholarPubMed
Lindvall, O, Kokaia, Z, Bengzon, J, Elmer, E, Kokaia, M (1994). Neurotrophins and brain insults. Trends in Neurosciences 17, 490496.CrossRefGoogle ScholarPubMed
Miyake, A, Friedman, NP, Emerson, MJ, Witzki, AH, Howerter, A, Wager, TD (2000). The unity and diversity of executive functions and their contributions to complex ‘Frontal Lobe’ tasks: a latent variable analysis. Cognitive Psychology 41, 49100.CrossRefGoogle ScholarPubMed
Monteleone, P, Fabrazzo, M, Martiadis, V, Serritella, C, Pannuto, M, Maj, M (2005). Circulating brain-derived neurotrophic factor is decreased in women with anorexia and bulimia nervosa but not in women with binge-eating disorder: relationships to co-morbid depression, psychopathology and hormonal variables. Psychological Medicine 35, 897905.CrossRefGoogle Scholar
Monteleone, P, Tortorella, A, Martiadis, V, Serritella, C, Fuscino, A, Maj, M (2004). Opposite changes in the serum brain-derived neurotrophic factor in anorexia nervosa and obesity. Psychosomatic Medicine 66, 744748.CrossRefGoogle ScholarPubMed
Nakazato, M, Hashimoto, K, Shimizu, E, Kumakiri, C, Koizumi, H, Okamura, N, Mitsumori, M, Komatsu, N, Iyo, M (2003). Decreased levels of serum brain-derived neurotrophic factor in female patients with eating disorders. Biological Psychiatry 54, 485490.CrossRefGoogle ScholarPubMed
Nakazato, M, Hashimoto, K, Yoshimura, K, Hashimoto, T, Shimizu, E, Iyo, M (2006). No change between the serum brain-derived neurotrophic factor in female patients with anorexia nervosa before and after partial weight recovery. Progress in Neuro-Psychopharmacology and Biological Psychiatry 30, 11171121.CrossRefGoogle ScholarPubMed
Pan, W, Banks, W, Fasold, M, Bluth, J, Kastin, A (1998). Transport of brain-derived neurotrophic factor across the blood–brain barrier. Neuropharmacology 37, 15531561.CrossRefGoogle ScholarPubMed
Ribases, M, Gratacos, M, Armengol, L, de Cid, R, Badia, A, Jimenez, L, Solano, R, Vallejo, J, Fernandez, F, Estivill, X (2003). Met66 in the brain-derived neurotrophic factor (BDNF) precursor is associated with anorexia nervosa restricting type. Molecular Psychiatry 8, 745751.CrossRefGoogle Scholar
Ribases, M, Gratacos, M, Fernandez-Aranda, F, Bellodi, L, Boni, C, Anderluh, M, Cavallini, MC, Cellini, E, Di Bella, D, Erzegovesi, S, Foulon, C, Gabrovsek, M, Gorwood, P, Hebebrand, J, Hinney, A, Holliday, J, Hu, X, Karwautz, A, Kipman, A, Komel, R, Nacmias, B, Remschmidt, H, Ricca, V, Sorbi, S, Tomori, M, Wagner, G, Treasure, J, Collier, DA, Estivill, X (2005). Association of BDNF with restricting anorexia nervosa and minimum body mass index: a family-based association study of eight European populations. European Journal of Human Genetics 13, 428434.CrossRefGoogle ScholarPubMed
Ribases, M, Gratacos, M, Fernandez-Aranda, F, Bellodi, L, Boni, C, Anderluh, M, Cavallini, MC, Cellini, E, Di Bella, D, Erzegovesi, S, Foulon, C, Gabrovsek, M, Gorwood, P, Hebebrand, J, Hinney, A, Holliday, J, Hu, X, Karwautz, A, Kipman, A, Komel, R, Nacmias, B, Remschmidt, H, Ricca, V, Sorbi, S, Wagner, G, Treasure, J, Collier, DA, Estivill, X (2004). Association of BDNF with anorexia nervosa, bulimia and age of onset of weight loss in six European populations. Human Molecular Genetics 13, 12051212.CrossRefGoogle ScholarPubMed
Rios, M, Fan, G, Fekete, C, Kelly, J, Bates, B, Kuehn, R, Lechan, RM, Jaenisch, R (2001). Conditional deletion of brain-derived neurotrophic factor in the postnatal brain leads to obesity and hyperactivity. Molecular Endocrinology 15, 17481757.CrossRefGoogle ScholarPubMed
Roberts, M, Tchanturia, K, Stahl, D, Southgate, L, Treasure, J (2007). A systematic review and meta-analysis of set-shifting ability in eating disorders. Psychological Medicine 37, 112.CrossRefGoogle ScholarPubMed
Rybakowski, J, Borkowska, A, Skibinska, M, Hauser, J (2006). Illness-specific association of val66met BDNF polymorphism with performance on Wisconsin Card Sorting Test in bipolar mood disorder. Molecular Psychiatry 11, 122124.CrossRefGoogle ScholarPubMed
Snider, W (1994). Functions of the neurotrophins during nervous system development: what the knockouts are teaching us. Cell 77, 627638.CrossRefGoogle ScholarPubMed
Southgate, L, Tchanturia, K, Treasure, J (2005). Building a model of the aetiology of eating disorders by translating experimental neuroscience into clinical practice. Journal of Mental Health 14, 553566.CrossRefGoogle Scholar
Steinglass, JE, Walsh, BT, Stern, Y (2006). Set shifting deficit in anorexia nervosa. Journal of the International Neuropsychological Society 12, 431435.CrossRefGoogle ScholarPubMed
Tchanturia, K, Campbell, IC, Morris, R, Treasure, J (2005). Neuropsychological studies in anorexia nervosa. International Journal of Eating Disorders 37, S72S76, discussion S87-S89.CrossRefGoogle ScholarPubMed
Tchanturia, K, Morris, R, Anderluh, B, Collier, D, Nikolaou, V, Treasure, J (2004). Set shifting in anorexia nervosa: an examination before and after weight gain, in full recovery and relationship to childhood and adult OCPD traits. Journal of Psychiatric Research 38, 545552.CrossRefGoogle ScholarPubMed
Thoenen, H (1995). Neurotrophins and neuronal plasticity. Science 270, 593598.CrossRefGoogle ScholarPubMed
Treasure, J, Southgate, L, Tchanturia, K, Lopez, C, Collier, D (2006). Gene environmental issues in eating disorders. Association for Child and Adolescent Mental Health 25, 5162.Google Scholar
Wagner, A, Barbarich-Marsteller, NC, Frank, GK, Bailer, UF, Wonderlich, SA, Crosby, RD, Henry, SE, Vogel, V, Plotnicov, K, McConaha, C, Kaye, WH (2006). Personality traits after recovery from eating disorders: do subtypes differ? International Journal of Eating Disorders 39, 276284.CrossRefGoogle ScholarPubMed
Zigmond, A, Snaith, R (1983). The Hospital Anxiety and Depression Scale. Acta Psychiatrica Scandinavica 67, 361370.CrossRefGoogle ScholarPubMed