Skip to main content
SpringerLink
Log in

Brain morphological changes in adolescent and adult patients with anorexia nervosa

  • Psychiatry and Preclinical Psychiatric Studies - Original Article
  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Abstract

Gray matter (GM) and white matter (WM) volume loss occur in the brains of patients with acute anorexia nervosa (AN) and improve again upon weight restoration. Adolescence is an important time period for AN to begin. However, little is known about the differences between brain changes in adolescents vs adults. We used a meta-analysis and a qualitative review of all MRI studies regarding acute structural brain volume changes and their recovery in adolescents and adults with AN. 29 studies with 473 acute, 121 short-term weight-recovered and 255 long-term recovered patients with AN were included in the meta-analysis. In acute AN, GM and WM were reduced compared to healthy controls. Acute adolescent patients showed a significantly greater GM reduction than adults (−8.4 vs −3.1 %), the difference in WM (−4.0 vs −2.1 %) did not reach significance. Short-term weight-recovered patients showed a remaining GM deficit of 3.6 % and a non-significant WM reduction of 0.9 % with no age differences. Following 1.5–8 years of remission, GM and WM were no longer significantly reduced in adults (GM −0.4 %, WM −0.7 %); long-term studies for adolescents were scarce. The qualitative review showed that GM volume loss was correlated with cognitive deficits and three studies found GM regions, cerebellar deficits and WM to be predictive of outcome. GM and WM are strongly reduced in acute AN and even more pronounced in adolescence. Long-term recovery appears to be complete for adults while no conclusions can be drawn for adolescents, thus caution remains.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Amianto F, Caroppo P, D’Agata F et al (2013) Brain volumetric abnormalities in patients with anorexia and bulimia nervosa: a voxel-based morphometry study. Psychiatry Res 213:210–216. doi:10.1016/j.pscychresns.2013.03.010

    Article  PubMed  Google Scholar 

  • Aoki C (2016) Synaptic changes in the hippocampus of adolescent female rodents associated with resilience to anxiety and suppression of food restriction-evoked hyperactivity in an animal model for anorexia nervosa. Brain Res. doi:10.1016/j.brainres.2016.01.019

    Google Scholar 

  • Bailer UF, Kaye WH (2011) Serotonin: imaging findings in eating disorders. Curr Top Behav Neurosci 6:59–79. doi:10.1007/7854_2010_78

    Article  PubMed  Google Scholar 

  • Banasr M, Dwyer JM, Duman RS (2011) Cell atrophy and loss in depression: reversal by antidepressant treatment. Curr Opin Cell Biol 23:730–737. doi:10.1016/j.ceb.2011.09.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bär K-J, de la Cruz F, Berger S et al (2015) Structural and functional differences in the cingulate cortex relate to disease severity in anorexia nervosa. J Psychiatry Neurosci JPN 40:269–279

    Article  PubMed  Google Scholar 

  • Barbarich-Marsteller NC, Fornal CA, Takase LF et al (2013) Activity-based anorexia is associated with reduced hippocampal cell proliferation in adolescent female rats. Behav Brain Res 236:251–257. doi:10.1016/j.bbr.2012.08.047

    Article  PubMed  Google Scholar 

  • Beadle JN, Paradiso S, Brumm M et al (2015) Larger hippocampus size in women with anorexia nervosa who exercise excessively than healthy women. Psychiatry Res 232:193–199. doi:10.1016/j.pscychresns.2014.10.013

    Article  PubMed  Google Scholar 

  • Benitez-Bribiesca L, De la R-A, Mansilla-Olivares A (1999) Dendritic spine pathology in infants with severe protein-calorie malnutrition. Pediatrics 104:e21

    Article  CAS  PubMed  Google Scholar 

  • Bodell LP, Keel PK, Brumm MC et al (2014) Longitudinal examination of decision-making performance in anorexia nervosa: before and after weight restoration. J Psychiatr Res 56:150–157. doi:10.1016/j.jpsychires.2014.05.015

    Article  PubMed  PubMed Central  Google Scholar 

  • Boghi A, Sterpone S, Sales S et al (2011) In vivo evidence of global and focal brain alterations in anorexia nervosa. Psychiatry Res 192:154–159

    Article  PubMed  Google Scholar 

  • Bomba M, Riva A, Veggo F et al (2013) Impact of speed and magnitude of weight loss on the development of brain trophic changes in adolescents with anorexia nervosa: a case control study. Ital J Pediatr 39:14. doi:10.1186/1824-7288-39-14

    Article  PubMed  PubMed Central  Google Scholar 

  • Bomba M, Riva A, Morzenti S et al (2015) Global and regional brain volumes normalization in weight-recovered adolescents with anorexia nervosa: preliminary findings of a longitudinal voxel-based morphometry study. Neuropsychiatr Dis Treat 11:637–645. doi:10.2147/NDT.S73239

    Article  PubMed  PubMed Central  Google Scholar 

  • Brooks SJ, Barker GJ, O’Daly OG et al (2011) Restraint of appetite and reduced regional brain volumes in anorexia nervosa: a voxel-based morphometric study. BMC Psychiatry 11:179. doi:10.1186/1471-244X-11-179

    Article  PubMed  PubMed Central  Google Scholar 

  • Buhren K, Holtkamp K, Herpertz-Dahlmann B, Konrad K (2008) Neuropsychological performance in anorexia and bulimia nervosa. ZKinder JugendpsychiatrPsychother 36:377–386

    Google Scholar 

  • Burkert NT, Koschutnig K, Ebner F, Freidl W (2015) Structural hippocampal alterations, perceived stress, and coping deficiencies in patients with anorexia nervosa. Int J Eat Disord 48:670–676. doi:10.1002/eat.22397

    Article  PubMed  Google Scholar 

  • Castro-Fornieles J, Bargallo N, Lazaro L et al (2009) A cross-sectional and follow-up voxel-based morphometric MRI study in adolescent anorexia nervosa. J Psychiatr Res 43:331–340

    Article  PubMed  Google Scholar 

  • Chui HT, Christensen BK, Zipursky RB et al (2008) Cognitive function and brain structure in females with a history of adolescent-onset anorexia nervosa. Pediatrics 122:e426–e437

    Article  PubMed  Google Scholar 

  • Connan F, Murphy F, Connor SE et al (2006) Hippocampal volume and cognitive function in anorexia nervosa. Psychiatry Res 146:117–125

    Article  PubMed  Google Scholar 

  • D’Agata F, Caroppo P, Amianto F et al (2015) Brain correlates of alexithymia in eating disorders: a voxel-based morphometry study. Psychiatry Clin Neurosci 69:708–716. doi:10.1111/pcn.12318

    Article  PubMed  Google Scholar 

  • Favaro A, Tenconi E, Degortes D et al (2014) Effects of obstetric complications on volume and functional connectivity of striatum in anorexia nervosa patients. Int J Eat Disord 47:686–695. doi:10.1002/eat.22320

    Article  PubMed  Google Scholar 

  • Favaro A, Tenconi E, Degortes D et al (2015) Gyrification brain abnormalities as predictors of outcome in anorexia nervosa. Hum Brain Mapp. doi:10.1002/hbm.22998

    PubMed  Google Scholar 

  • Fonville L, Giampietro V, Williams SCR et al (2013) Alterations in brain structure in adults with anorexia nervosa and the impact of illness duration. Psychol Med 44:1965–1975. doi:10.1017/S0033291713002389

    Article  PubMed  Google Scholar 

  • Fonville L, Giampietro V, Williams SCR et al (2014) Alterations in brain structure in adults with anorexia nervosa and the impact of illness duration. Psychol Med 44:1965–1975. doi:10.1017/S0033291713002389

    Article  CAS  PubMed  Google Scholar 

  • Frank GKW (2014) Could dopamine agonists aid in drug development for anorexia nervosa? Front Nutr 1:19. doi:10.3389/fnut.2014.00019

    Article  PubMed  PubMed Central  Google Scholar 

  • Frank GK, Shott ME, Hagman JO, Mittal VA (2013) Alterations in brain structures related to taste reward circuitry in ill and recovered anorexia nervosa and in bulimia nervosa. Am J Psychiatry 170:1152–1160. doi:10.1176/appi.ajp.2013.12101294

    Article  PubMed  PubMed Central  Google Scholar 

  • Friederich H-C, Herzog W (2011) Cognitive-behavioral flexibility in anorexia nervosa. Curr Top Behav Neurosci 6:111–123. doi:10.1007/7854_2010_83

    Article  PubMed  Google Scholar 

  • Friederich HC, Walther S, Bendszus M et al (2012) Grey matter abnormalities within cortico-limbic-striatal circuits in acute and weight-restored anorexia nervosa patients. Neuroimage 59:1106–1113

    Article  PubMed  Google Scholar 

  • Fuglset TS, Endestad T, Landrø NI, Rø Ø (2015) Brain structure alterations associated with weight changes in young females with anorexia nervosa: a case series. Neurocase 21:169–177. doi:10.1080/13554794.2013.878728

    Article  PubMed  Google Scholar 

  • Fujisawa TX, Yatsuga C, Mabe H et al (2015) Anorexia Nervosa during Adolescence Is Associated with Decreased Gray Matter Volume in the Inferior Frontal Gyrus. PloS One 10:e0128548. doi:10.1371/journal.pone.0128548

    Article  PubMed  PubMed Central  Google Scholar 

  • Garcia-Ruiz M, Diaz-Cintra S, Cintra L, Corkidi G (1993) Effect of protein malnutrition on CA3 hippocampal pyramidal cells in rats of three ages. Brain Res 625:203–212

    Article  CAS  PubMed  Google Scholar 

  • Gaudio S, Nocchi F, Franchin T et al (2011) Gray matter decrease distribution in the early stages of Anorexia Nervosa restrictive type in adolescents. Psychiatry Res 191:24–30

    Article  PubMed  Google Scholar 

  • Gibson KR, Petersen AC (1991) Brain maturation and cognitive development: comparative and cross-cultural perspectives. Transaction Publishers

  • Giordano GD, Renzetti P, Parodi RC et al (2001) Volume measurement with magnetic resonance imaging of hippocampus-amygdala formation in patients with anorexia nervosa. J Endocrinol Invest 24:510–514

    Article  CAS  PubMed  Google Scholar 

  • Herpertz-Dahlmann B (2015) Adolescent eating disorders: update on definitions, symptomatology, epidemiology, and comorbidity. Child Adolesc Psychiatr Clin N Am 24:177–196. doi:10.1016/j.chc.2014.08.003

    Article  PubMed  Google Scholar 

  • Joos A, Kloppel S, Hartmann A et al (2010) Voxel-based morphometry in eating disorders: correlation of psychopathology with grey matter volume. Psychiatry Res 182:146–151

    Article  PubMed  Google Scholar 

  • Joos AAB, Perlov E, Büchert M et al (2011a) Magnetic resonance spectroscopy of the anterior cingulate cortex in eating disorders. Psychiatry Res 191:196–200. doi:10.1016/j.pscychresns.2010.10.004

    Article  PubMed  Google Scholar 

  • Joos A, Hartmann A, Glauche V et al (2011b) Grey matter deficit in long-term recovered anorexia nervosa patients. Eur Eat Disord Rev J Eat Disord Assoc 19:59–63. doi:10.1002/erv.1060

    Article  Google Scholar 

  • Joos A, Saum B, Hartmann A et al (2012) Distinct functional and structural cerebral abnormalities in eating disorders in the light of diagnostic classification systems. Psychother Psychosom 81:394–395. doi:10.1159/000337747

    Article  PubMed  Google Scholar 

  • Katzman DK, Lambe EK, Mikulis DJ, et al (1996) Cerebral gray matter and white matter volume deficits in adolescent girls with anorexia nervosa. J Pediatr 129:794–803

    Article  CAS  PubMed  Google Scholar 

  • Katzman DK, Zipursky RB, Lambe EK, Mikulis DJ (1997) A longitudinal magnetic resonance imaging study of brain changes in adolescents with anorexia nervosa. Arch Pediatr Adolesc Med 151:793–797

    Article  CAS  PubMed  Google Scholar 

  • King JA, Geisler D, Ritschel F et al (2015) Global cortical thinning in acute anorexia nervosa normalizes following long-term weight restoration. Biol Psychiatry 77:624–632. doi:10.1016/j.biopsych.2014.09.005

    Article  PubMed  Google Scholar 

  • Kochunov P, Glahn DC, Lancaster J et al (2011) Fractional anisotropy of cerebral white matter and thickness of cortical gray matter across the lifespan. NeuroImage 58:41–49. doi:10.1016/j.neuroimage.2011.05.050

    Article  CAS  PubMed  Google Scholar 

  • Lambe EK, Katzman DK, Mikulis DJ, et al (1997) Cerebral gray matter volume deficits after weight recovery from anorexia nervosa. Arch Gen Psychiatry 54:537–542

    Article  CAS  PubMed  Google Scholar 

  • Lang K, Stahl D, Espie J et al (2014) Set shifting in children and adolescents with anorexia nervosa: an exploratory systematic review and meta-analysis. Int J Eat Disord 47:394–399. doi:10.1002/eat.22235

    Article  PubMed  Google Scholar 

  • Lazaro L, Andres S, Calvo A, et al (2013) Normal gray and white matter volume after weight restoration in adolescents with anorexia nervosa. Int J Eat Disord 46:841–848. doi:10.1002/eat.22161

    Article  PubMed  Google Scholar 

  • Lenroot RK, Giedd JN (2006) Brain development in children and adolescents: insights from anatomical magnetic resonance imaging. Neurosci Biobehav Rev 30:718–729. doi:10.1016/j.neubiorev.2006.06.001

    Article  PubMed  Google Scholar 

  • Mainz V, Schulte-Rüther M, Fink GR et al (2012) Structural brain abnormalities in adolescent anorexia nervosa before and after weight recovery and associated hormonal changes. Psychosom Med 74:574–582. doi:10.1097/PSY.0b013e31824ef10e

    Article  PubMed  Google Scholar 

  • McCormick LM, Keel PK, Brumm MC et al (2008) Implications of starvation-induced change in right dorsal anterior cingulate volume in anorexia nervosa. Int J Eat Disord 41:602–610

    Article  PubMed  PubMed Central  Google Scholar 

  • Mühlau M, Gaser C, Ilg R et al (2007) Gray matter decrease of the anterior cingulate cortex in anorexia nervosa. AmJPsychiatry 164:1850–1857

    Google Scholar 

  • Murrin LC, Sanders JD, Bylund DB (2007) Comparison of the maturation of the adrenergic and serotonergic neurotransmitter systems in the brain: implications for differential drug effects on juveniles and adults. Biochem Pharmacol 73:1225–1236. doi:10.1016/j.bcp.2007.01.028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nagahara Y, Nakamae T, Nishizawa S et al (2014) A tract-based spatial statistics study in anorexia nervosa: abnormality in the fornix and the cerebellum. Prog Neuropsychopharmacol Biol Psychiatry 51:72–77. doi:10.1016/j.pnpbp.2014.01.009

    Article  PubMed  Google Scholar 

  • Neumärker KJ, Dudeck U, Meyer U et al (1997) Anorexia nervosa and sudden death in childhood: clinical data and results obtained from quantitative neurohistological investigations of cortical neurons. Eur Arch Psychiatry Clin Neurosci 247:16–22

    Article  PubMed  Google Scholar 

  • Nogal P, Pniewska-Siark B, Lewinski A (2008) Relation of trophic changes in the central nervous system, measured by the width of cordical sulci, to the clinical course of anorexia nervosa (II). NeuroEndocrinolLett 29:879–883

    CAS  Google Scholar 

  • Reyes-Haro D, Labrada-Moncada FE, Miledi R, Martínez-Torres A (2015) Dehydration-induced anorexia reduces astrocyte density in the rat corpus callosum. Neural Plast 2015:474917. doi:10.1155/2015/474917

    PubMed  PubMed Central  Google Scholar 

  • Roberto CA, Mayer LE, Brickman AM, et al (2011) Brain tissue volume changes following weight gain in adults with anorexia nervosa. Int J Eat Disord 44:406–411

    Article  PubMed  Google Scholar 

  • Schmahmann JD, Weilburg JB, Sherman JC (2007) The neuropsychiatry of the cerebellum—insights from the clinic. Cerebellum Lond Engl 6:254–267. doi:10.1080/14734220701490995

    Article  Google Scholar 

  • Seitz J, Bühren K, von Polier GG et al (2014) Morphological changes in the brain of acutely ill and weight-recovered patients with anorexia nervosa. A meta-analysis and qualitative review. Z Für Kinder- Jugendpsychiatrie Psychother 42:7–17. doi:10.1024/1422-4917/a000265 (quiz 17–18)

    Article  Google Scholar 

  • Seitz J, Walter M, Mainz V et al (2015) Brain volume reduction predicts weight development in adolescent patients with anorexia nervosa. J Psychiatr Res 68:228–237. doi:10.1016/j.jpsychires.2015.06.019

    Article  PubMed  Google Scholar 

  • Shaw P, Kabani NJ, Lerch JP et al (2008) Neurodevelopmental trajectories of the human cerebral cortex. J Neurosci Off J Soc Neurosci 28:3586–3594. doi:10.1523/JNEUROSCI.5309-07.2008

    Article  CAS  Google Scholar 

  • Shott ME, Pryor TL, Yang TT, Frank GKW (2015) Greater insula white matter fiber connectivity in women Recovered from anorexia nervosa. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol. doi:10.1038/npp.2015.172

    Google Scholar 

  • Steen RG, Hamer RM, Lieberman JA (2007) Measuring brain volume by MR imaging: impact of measurement precision and natural variation on sample size requirements. AJNR Am J Neuroradiol 28:1119–1125. doi:10.3174/ajnr.A0537

    Article  CAS  PubMed  Google Scholar 

  • Steinhausen HC (2009) Outcome of eating disorders. Child Adolesc Psychiatr Clin N Am 18:225–242

    Article  PubMed  Google Scholar 

  • Suchan B, Busch M, Schulte D et al (2010) Reduction of gray matter density in the extrastriate body area in women with anorexia nervosa. Behav Brain Res 206:63–67

    Article  PubMed  Google Scholar 

  • Swayze VW, Andersen AE, Andreasen NC et al (2003) Brain tissue volume segmentation in patients with anorexia nervosa before and after weight normalization. Int J Eat Disord 33:33–44

    Article  PubMed  Google Scholar 

  • Tchanturia K, Morris RG, Anderluh MB et al (2004) Set shifting in anorexia nervosa: an examination before and after weight gain, in full recovery and relationship to childhood and adult OCPD traits. J Psychiatr Res 38:545–552

    Article  CAS  PubMed  Google Scholar 

  • Titova OE, Hjorth OC, Schiöth HB, Brooks SJ (2013) Anorexia nervosa is linked to reduced brain structure in reward and somatosensory regions: a meta-analysis of VBM studies. BMC Psychiatry 13:110. doi:10.1186/1471-244X-13-110

    Article  PubMed  PubMed Central  Google Scholar 

  • Van den Eynde F, Suda M, Broadbent H et al (2012) Structural magnetic resonance imaging in eating disorders: a systematic review of voxel-based morphometry studies. Eur Eat Disord Rev J Eat Disord Assoc 20:94–105. doi:10.1002/erv.1163

    Article  Google Scholar 

  • van Opstal AM, Westerink AM, Teeuwisse WM et al (2015) Hypothalamic BOLD response to glucose intake and hypothalamic volume are similar in anorexia nervosa and healthy control subjects. Front Neurosci 9:159. doi:10.3389/fnins.2015.00159

    PubMed  PubMed Central  Google Scholar 

  • Via E, Zalesky A, Sánchez I, et al (2014) Disruption of brain white matter microstructure in women with anorexia nervosa. J Psychiatry Neurosci JPN 39:130135

    Article  Google Scholar 

  • Vocks S, Schulte D, Busch M et al (2011) Changes in neuronal correlates of body image processing by means of cognitive-behavioural body image therapy for eating disorders: a randomized controlled fMRI study. Psychol Med 41:1651–1663. doi:10.1017/S0033291710002382

    Article  CAS  PubMed  Google Scholar 

  • Wagner A, Greer P, Bailer UF, et al (2006) Normal brain tissue volumes after long-term recovery in anorexia and bulimia nervosa. Biol Psychiatry 59:291–293

    Article  PubMed  Google Scholar 

  • Yau WY, Bischoff-Grethe A, Theilmann RJ et al (2013) Alterations in white matter microstructure in women recovered from anorexia nervosa. Int J Eat Disord 46:701–708. doi:10.1002/eat.22154

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatics, University Hospital RWTH University Aachen, Neuenhofer Weg 21, 52074, Aachen, Germany

    J. Seitz, B. Herpertz-Dahlmann & K. Konrad

Authors
  1. J. Seitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. Herpertz-Dahlmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K. Konrad
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. Seitz.

Ethics declarations

Funding

This study was funded by internal board funds.

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

702_2016_1567_MOESM1_ESM.pdf

RevMan 5.3 results for GM, WM and CSF for acutely ill AN compared to HC (Supp Fig. 1–3), short term recovered compared to HC (Supp Fig. 4–6) and longterm recovered AN compared to HC (Supp Fig. 7–9). For studies where brain volumes correction for ICV was possible, means indicate % of ICV. For studies without brain volume correction, means indicate mm3 brain volume. (PDF 1899 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Seitz, J., Herpertz-Dahlmann, B. & Konrad, K. Brain morphological changes in adolescent and adult patients with anorexia nervosa. J Neural Transm 123, 949–959 (2016). https://doi.org/10.1007/s00702-016-1567-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-016-1567-9

Keywords

Search

Navigation