Skip to main content
Log in

Role of FKBP5 in emotion processing: results on amygdala activity, connectivity and volume

  • Original Article
  • Published:
Brain Structure and Function Aims and scope Submit manuscript

Abstract

Accumulating evidence suggests a role of FKBP5, a co-chaperone regulating the glucocorticoid receptor sensitivity, in the etiology of depression and anxiety disorders. Based on recent findings of altered amygdala activity following childhood adversity, the present study aimed at clarifying the impact of genetic variation in FKBP5 on threat-related neural activity and coupling as well as morphometric alterations in stress-sensitive brain systems. Functional magnetic resonance imaging during an emotional face-matching task was performed in 153 healthy young adults (66 males) from a high-risk community sample followed since birth. Voxel-based morphometry was applied to study structural alterations and DNA was genotyped for FKBP5 rs1360780. Childhood adversity was measured using retrospective self-report (Childhood Trauma Questionnaire) and by a standardized parent interview assessing childhood family adversity. Depression was assessed by the Beck Depression Inventory. There was a main effect of FKBP5 on the left amygdala, with T homozygotes showing the highest activity, largest volume and increased coupling with the left hippocampus and the orbitofrontal cortex (OFC). Moreover, amygdala-OFC coupling proved to be associated with depression in this genotype. In addition, our results support previous evidence of a gene-environment interaction on right amygdala activity with respect to retrospective assessment of childhood adversity, but clarify that this does not generalize to the prospective assessment. These findings indicated that activity in T homozygotes increased with the level of adversity, whereas the opposite pattern emerged in C homozygotes, with CT individuals being intermediate. The present results point to a functional involvement of FKBP5 in intermediate phenotypes associated with emotional processing, suggesting a possible mechanism for this gene in conferring susceptibility to stress-related disorders.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Altshuler LL, Bartzokis G, Grieder T, Curran J, Mintz J (1998) Amygdala enlargement in bipolar disorder and hippocampal reduction in schizophrenia: an MRI study demonstrating neuroanatomic specificity. Arch Gen Psychiatry 55:663–664

    CAS  PubMed  Google Scholar 

  • Anacker C, Zunszain PA, Carvalho LA, Pariante CM (2011) The glucocorticoid receptor: pivot of depression and of antidepressant treatment? Psychoneuroendocrinology 36:415–425. doi:10.1016/j.psyneuen.2010.03.007

    PubMed Central  CAS  PubMed  Google Scholar 

  • Anand A, Li Y, Wang Y, Wu J, Gao S, Bukhari L et al (2005) Activity and connectivity of brain mood regulating circuit in depression: a functional magnetic resonance study. Biol Psychiatry 57:1079–1088. doi:10.1016/j.biopsych.2005.02.021

    PubMed  Google Scholar 

  • Appel K, Schwahn C, Mahler J, Schulz A, Spitzer C, Fenske K et al (2011) Moderation of adult depression by a polymorphism in the FKBP5 gene and childhood physical abuse in the general population. Neuropsychopharmacology 36:1982–1991. doi:10.1038/npp.2011.81

    PubMed Central  PubMed  Google Scholar 

  • Aron AR, Robbins TW, Poldrack RA (2004) Inhibition and the right inferior frontal cortex. Trends Cogn Sci 8:170–177. doi:10.1016/j.tics.2004.02.010

    PubMed  Google Scholar 

  • Ashburner J (2007) A fast diffeomorphic image registration algorithm. Neuroimage 38:95–113. doi:10.1016/j.neuroimage.2007.07.007

    PubMed  Google Scholar 

  • Baas D, Aleman A, Kahn RS (2004) Lateralization of amygdala activation: a systematic review of functional neuroimaging studies. Brain Res Brain Res Rev 45:96–103. doi:10.1016/j.brainresrev.2004.02.004

    PubMed  Google Scholar 

  • Bernstein DP, Stein JA, Newcomb MD, Walker E, Pogge D, Ahluvalia T et al (2003) Development and validation of a brief screening version of the childhood trauma questionnaire. Child Abuse Negl 27:169–190

    PubMed  Google Scholar 

  • Binder EB (2009) The role of FKBP5, a co-chaperone of the glucocorticoid receptor in the pathogenesis and therapy of affective and anxiety disorders. Psychoneuroendocrinology 34(Suppl 1):S186–S195

    CAS  PubMed  Google Scholar 

  • Binder EB, Salyakina D, Lichtner P, Wochnik GM, Ising M, Putz B et al (2004) Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment. Nat Genet 36:1319–1325

    CAS  PubMed  Google Scholar 

  • Binder EB, Bradley RG, Liu W, Epstein MP, Deveau TC, Mercer KB et al (2008) Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA 299:1291–1305

    PubMed Central  CAS  PubMed  Google Scholar 

  • Bradley BP, Mogg K, Millar N (1996) Implicit memory bias in clinical and non-clinical depression. Behav Res Ther 34:865–879

    CAS  PubMed  Google Scholar 

  • Bremner JD, Narayan M, Anderson ER, Staib LH, Miller HL, Charney DS (2000) Hippocampal volume reduction in major depression. Am J Psychiatry 157:115–118

    CAS  PubMed  Google Scholar 

  • Brent D, Melhem N, Ferrell R, Emslie G, Wagner KD, Ryan N et al (2010) Association of FKBP5 polymorphisms with suicidal events in the Treatment of Resistant Depression in Adolescents (TORDIA) study. Am J Psychiatry 167:190–197. doi:10.1176/appi.ajp.2009.09040576

    PubMed Central  PubMed  Google Scholar 

  • Buchmann AF, Holz N, Boecker R, Blomeyer D, Rietschel M, Witt SH et al (2013) Moderating role of FKBP5 genotype in the impact of childhood adversity on cortisol stress response during adulthood. Eur Neuropsychopharmacol. doi:10.1016/j.euroneuro.2013.12.001

    Google Scholar 

  • Buckholtz JW, Callicott JH, Kolachana B, Hariri AR, Goldberg TE, Genderson M et al (2008) Genetic variation in MAOA modulates ventromedial prefrontal circuitry mediating individual differences in human personality. Mol Psychiatry 13:313–324

    CAS  PubMed  Google Scholar 

  • Buss C, Davis EP, Shahbaba B, Pruessner JC, Head K, Sandman CA (2012) Maternal cortisol over the course of pregnancy and subsequent child amygdala and hippocampus volumes and affective problems. Proc Natl Acad Sci USA 109:E1312–E1319. doi:10.1073/pnas.1201295109

    PubMed Central  CAS  PubMed  Google Scholar 

  • Cahill L, Haier RJ, Fallon J, Alkire MT, Tang C, Keator D et al (1996) Amygdala activity at encoding correlated with long-term, free recall of emotional information. Proc Natl Acad Sci USA 93:8016–8021

    PubMed Central  CAS  PubMed  Google Scholar 

  • Canli T, Zhao Z, Brewer J, Gabrieli JD, Cahill L (2000) Event-related activation in the human amygdala associates with later memory for individual emotional experience. J Neurosci 20:RC99

    CAS  PubMed  Google Scholar 

  • Carballedo A, Scheuerecker J, Meisenzahl E, Schoepf V, Bokde A, Moller HJ et al (2011) Functional connectivity of emotional processing in depression. J Affect Disord 134:272–279. doi:10.1016/j.jad.2011.06.021

    PubMed  Google Scholar 

  • Carey PD, Walker JL, Rossouw W, Seedat S, Stein DJ (2008) Risk indicators and psychopathology in traumatised children and adolescents with a history of sexual abuse. Eur Child Adolesc Psychiatry 17:93–98. doi:10.1007/s00787-007-0641-0

    PubMed  Google Scholar 

  • Cavada C, Company T, Tejedor J, Cruz-Rizzolo RJ, Reinoso-Suarez F (2000) The anatomical connections of the macaque monkey orbitofrontal cortex. A review. Cereb Cortex 10:220–242

    CAS  PubMed  Google Scholar 

  • Costafreda SG, McCann P, Saker P, Cole JH, Cohen-Woods S, Farmer AE et al (2013) Modulation of amygdala response and connectivity in depression by serotonin transporter polymorphism and diagnosis. J Affect Disord 150:96–103. doi:10.1016/j.jad.2013.02.028

    CAS  PubMed  Google Scholar 

  • Davis M, Whalen PJ (2001) The amygdala: vigilance and emotion. Mol Psychiatry 6:13–34

    CAS  PubMed  Google Scholar 

  • de Quervain DJ, Roozendaal B, McGaugh JL (1998) Stress and glucocorticoids impair retrieval of long-term spatial memory. Nature 394:787–790. doi:10.1038/29542

    PubMed  Google Scholar 

  • de Quervain DJ, Aerni A, Schelling G, Roozendaal B (2009) Glucocorticoids and the regulation of memory in health and disease. Front Neuroendocrinol 30:358–370. doi:10.1016/j.yfrne.2009.03.002

    PubMed  Google Scholar 

  • Demenescu LR, Kortekaas R, Cremers HR, Renken RJ, van Tol MJ, van der Wee NJ et al (2013) Amygdala activation and its functional connectivity during perception of emotional faces in social phobia and panic disorder. J Psychiatr Res 47:1024–1031. doi:10.1016/j.jpsychires.2013.03.020

    CAS  PubMed  Google Scholar 

  • Denny WB, Valentine DL, Reynolds PD, Smith DF, Scammell JG (2000) Squirrel monkey immunophilin FKBP51 is a potent inhibitor of glucocorticoid receptor binding. Endocrinology 141:4107–4113

    CAS  PubMed  Google Scholar 

  • Dolcos F, LaBar KS, Cabeza R (2004) Dissociable effects of arousal and valence on prefrontal activity indexing emotional evaluation and subsequent memory: an event-related fMRI study. Neuroimage 23:64–74. doi:10.1016/j.neuroimage.2004.05.015

    PubMed  Google Scholar 

  • Dolcos F, LaBar KS, Cabeza R (2005) Remembering one year later: role of the amygdala and the medial temporal lobe memory system in retrieving emotional memories. Proc Natl Acad Sci USA 102:2626–2631. doi:10.1073/pnas.0409848102

    PubMed Central  CAS  PubMed  Google Scholar 

  • Drabant EM, Hariri AR, Meyer-Lindenberg A, Munoz KE, Mattay VS, Kolachana BS et al (2006) Catechol O-methyltransferase val158met genotype and neural mechanisms related to affective arousal and regulation. Arch Gen Psychiatry 63:1396–1406

    CAS  PubMed  Google Scholar 

  • Drevets WC, Price JL, Furey ML (2008) Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression. Brain Struct Funct 213:93–118. doi:10.1007/s00429-008-0189-x

    PubMed Central  PubMed  Google Scholar 

  • Ekman P, Friesen W (1979) Pictures of facial affect. Consulting Psychologist Press, San Francisco

    Google Scholar 

  • Etkin A, Wager TD (2007) Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. Am J Psychiatry 164:1476–1488

    PubMed Central  PubMed  Google Scholar 

  • Fani N, Gutman D, Tone EB, Almli L, Mercer KB, Davis J et al (2013) FKBP5 and attention bias for threat: associations with hippocampal function and shape. JAMA Psychiatry1–9. doi:10.1001/2013.jamapsychiatry.210

  • Feldman S, Weidenfeld J (1998) The excitatory effects of the amygdala on hypothalamo-pituitary-adrenocortical responses are mediated by hypothalamic norepinephrine, serotonin, and CRF-41. Brain Res Bull 45:389–393 [pii] S0361-9230(97)00384-5

    CAS  PubMed  Google Scholar 

  • Friston KJ, Buechel C, Fink GR, Morris J, Rolls E, Dolan RJ (1997) Psychophysiological and modulatory interactions in neuroimaging. Neuroimage 6:218–229. doi:10.1006/nimg.1997.0291

    CAS  PubMed  Google Scholar 

  • Ghosh S, Laxmi TR, Chattarji S (2013) Functional connectivity from the amygdala to the hippocampus grows stronger after stress. J Neurosci 33:7234–7244. doi:10.1523/JNEUROSCI.0638-13.2013

    CAS  PubMed  Google Scholar 

  • Gottesman II, Gould TD (2003) The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 160:636–645

    PubMed  Google Scholar 

  • Hamann SB, Ely TD, Grafton ST, Kilts CD (1999) Amygdala activity related to enhanced memory for pleasant and aversive stimuli. Nat Neurosci 2:289–293. doi:10.1038/6404

    CAS  PubMed  Google Scholar 

  • Hamilton JP, Gotlib IH (2008) Neural substrates of increased memory sensitivity for negative stimuli in major depression. Biol Psychiatry 63:1155–1162. doi:10.1016/j.biopsych.2007.12.015

    PubMed Central  PubMed  Google Scholar 

  • Hariri AR, Tessitore A, Mattay VS, Fera F, Weinberger DR (2002) The amygdala response to emotional stimuli: a comparison of faces and scenes. Neuroimage 17:317–323

    PubMed  Google Scholar 

  • Hastings RS, Parsey RV, Oquendo MA, Arango V, Mann JJ (2004) Volumetric analysis of the prefrontal cortex, amygdala, and hippocampus in major depression. Neuropsychopharmacology 29:952–959. doi:10.1038/sj.npp.1300371

    PubMed  Google Scholar 

  • Hauger RL, Olivares-Reyes JA, Dautzenberg FM, Lohr JB, Braun S, Oakley RH (2012) Molecular and cell signaling targets for PTSD pathophysiology and pharmacotherapy. Neuropharmacology 62:705–714. doi:10.1016/j.neuropharm.2011.11.007

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hautzinger M, Bailer M, Worall H, Keller F (1994) Beck-Depressions-Inventar (BDI) (in German). Hans Huber, Bern

    Google Scholar 

  • Henckens MJ, van Wingen GA, Joels M, Fernandez G (2010) Time-dependent effects of corticosteroids on human amygdala processing. J Neurosci 30:12725–12732. doi:10.1523/JNEUROSCI.3112-10.2010

    CAS  PubMed  Google Scholar 

  • Hooker CI, Verosky SC, Germine LT, Knight RT, D’Esposito M (2008) Mentalizing about emotion and its relationship to empathy. Soc Cogn Affect Neurosci 3:204–217. doi:10.1093/scan/nsn019

    PubMed Central  PubMed  Google Scholar 

  • Huang MC, Schwandt ML, Ramchandani VA, George DT, Heilig M (2012) Impact of multiple types of childhood trauma exposure on risk of psychiatric comorbidity among alcoholic inpatients. Alcohol Clin Exp Res 36:1099–1107. doi:10.1111/j.1530-0277.2011.01695.x

    CAS  PubMed  Google Scholar 

  • Ikegaya Y, Saito H, Abe K (1996) The basomedial and basolateral amygdaloid nuclei contribute to the induction of long-term potentiation in the dentate gyrus in vivo. Eur J Neurosci 8:1833–1839

    CAS  PubMed  Google Scholar 

  • Ising M, Depping AM, Siebertz A, Lucae S, Unschuld PG, Kloiber S et al (2008) Polymorphisms in the FKBP5 gene region modulate recovery from psychosocial stress in healthy controls. Eur J Neurosci 28:389–398

    PubMed  Google Scholar 

  • Johnson LR, Farb C, Morrison JH, McEwen BS, LeDoux JE (2005) Localization of glucocorticoid receptors at postsynaptic membranes in the lateral amygdala. Neuroscience 136:289–299. doi:10.1016/j.neuroscience.2005.06.050

    CAS  PubMed  Google Scholar 

  • Kanske P, Heissler J, Schonfelder S, Bongers A, Wessa M (2011) How to regulate emotion? Neural networks for reappraisal and distraction. Cereb Cortex 21:1379–1388. doi:10.1093/cercor/bhq216

    PubMed  Google Scholar 

  • Kim MJ, Loucks RA, Palmer AL, Brown AC, Solomon KM, Marchante AN et al (2011) The structural and functional connectivity of the amygdala: from normal emotion to pathological anxiety. Behav Brain Res 223:403–410. doi:10.1016/j.bbr.2011.04.025

    PubMed Central  PubMed  Google Scholar 

  • Konishi S, Nakajima K, Uchida I, Kikyo H, Kameyama M, Miyashita Y (1999) Common inhibitory mechanism in human inferior prefrontal cortex revealed by event-related functional MRI. Brain 122(Pt 5):981–991

    PubMed  Google Scholar 

  • Kounou KB, Bui E, Dassa KS, Hinton D, Fischer L, Djassoa G et al (2013) Childhood trauma, personality disorders symptoms and current major depressive disorder in Togo. Soc Psychiatry Psychiatr Epidemiol 48:1095–1103. doi:10.1007/s00127-012-0634-2

    PubMed  Google Scholar 

  • Kuo JR, Kaloupek DG, Woodward SH (2012) Amygdala volume in combat-exposed veterans with and without posttraumatic stress disorder: a cross-sectional study. Arch Gen Psychiatry 69:1080–1086. doi:10.1001/archgenpsychiatry.2012.73

    PubMed  Google Scholar 

  • LaBar KS, Cabeza R (2006) Cognitive neuroscience of emotional memory. Nat Rev Neurosci 7:54–64. doi:10.1038/nrn1825

    CAS  PubMed  Google Scholar 

  • Lange C, Irle E (2004) Enlarged amygdala volume and reduced hippocampal volume in young women with major depression. Psychol Med 34:1059–1064

    CAS  PubMed  Google Scholar 

  • Laucht M, Esser G, Schmidt MH (1997) Developmental outcome of infants born with biological and psychosocial risks. J Child Psychol Psychiatry 38:843–853

    CAS  PubMed  Google Scholar 

  • Laucht M, Esser G, Baving L, Gerhold M, Hoesch I, Ihle W et al (2000) Behavioral sequelae of perinatal insults and early family adversity at 8 years of age. J Am Acad Child Adolesc Psychiatry 39:1229–1237

    CAS  PubMed  Google Scholar 

  • Laucht M, Treutlein J, Blomeyer D, Buchmann AF, Schmidt MH, Esser G et al (2012) Interactive effects of corticotropin-releasing hormone receptor 1 gene and childhood adversity on depressive symptoms in young adults: findings from a longitudinal study. Eur Neuropsychopharmacol. doi:10.1016/j.euroneuro.2012.06.002

    Google Scholar 

  • Lavebratt C, Aberg E, Sjoholm LK, Forsell Y (2010) Variations in FKBP5 and BDNF genes are suggestively associated with depression in a Swedish population-based cohort. J Affect Disord 125:249–255. doi:10.1016/j.jad.2010.02.113

    CAS  PubMed  Google Scholar 

  • LeDoux JE (2000) Emotion circuits in the brain. Annu Rev Neurosci 23:155–184. doi:10.1146/annurev.neuro.23.1.155

    CAS  PubMed  Google Scholar 

  • Lekman M, Laje G, Charney D, Rush AJ, Wilson AF, Sorant AJ et al (2008) The FKBP5-gene in depression and treatment response—an association study in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Cohort. Biol Psychiatry 63:1103–1110

    PubMed Central  CAS  PubMed  Google Scholar 

  • Levesque J, Eugene F, Joanette Y, Paquette V, Mensour B, Beaudoin G et al (2003) Neural circuitry underlying voluntary suppression of sadness. Biol Psychiatry 53:502–510 [pii] S0006322302018176

    PubMed  Google Scholar 

  • Levy-Gigi E, Szabo C, Kelemen O, Keri S (2013) Association among clinical response, hippocampal volume, and FKBP5 Gene expression in individuals with posttraumatic stress disorder receiving cognitive behavioral therapy. Biol Psychiatry 74:793–800. doi:10.1016/j.biopsych.2013.05.017

    CAS  PubMed  Google Scholar 

  • Lieberman MD, Eisenberger NI, Crockett MJ, Tom SM, Pfeifer JH, Way BM (2007) Putting feelings into words: affect labeling disrupts amygdala activity in response to affective stimuli. Psychol Sci 18:421–428. doi:10.1111/j.1467-9280.2007.01916.x

    PubMed  Google Scholar 

  • Lorenzetti V, Allen NB, Whittle S, Yucel M (2010) Amygdala volumes in a sample of current depressed and remitted depressed patients and healthy controls. J Affect Disord 120:112–119. doi:10.1016/j.jad.2009.04.021

    PubMed  Google Scholar 

  • Lupien SJ, Parent S, Evans AC, Tremblay RE, Zelazo PD, Corbo V et al (2011) Larger amygdala but no change in hippocampal volume in 10-year-old children exposed to maternal depressive symptomatology since birth. Proc Natl Acad Sci USA 108:14324–14329. doi:10.1073/pnas.1105371108

    PubMed Central  CAS  PubMed  Google Scholar 

  • Maldjian JA, Laurienti PJ, Kraft RA, Burdette JH (2003) An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. Neuroimage 19:1233–1239

    PubMed  Google Scholar 

  • Meyer-Lindenberg A, Weinberger DR (2006) Intermediate phenotypes and genetic mechanisms of psychiatric disorders. Nat Rev Neurosci 7:818–827

    CAS  PubMed  Google Scholar 

  • Meyer-Lindenberg A, Hariri AR, Munoz KE, Mervis CB, Mattay VS, Morris CA et al (2005) Neural correlates of genetically abnormal social cognition in Williams syndrome. Nat Neurosci 8:991–993

    CAS  PubMed  Google Scholar 

  • Meyer-Lindenberg A, Buckholtz JW, Kolachana B, Hariri R, Pezawas L, Blasi G et al (2006) Neural mechanisms of genetic risk for impulsivity and violence in humans. Proc Natl Acad Sci USA 103:6269–6274

    PubMed Central  CAS  PubMed  Google Scholar 

  • Mier D, Kirsch P, Meyer-Lindenberg A (2010) Neural substrates of pleiotropic action of genetic variation in COMT: a meta-analysis. Mol Psychiatry 15:918–927

    CAS  PubMed  Google Scholar 

  • Morey RA, Gold AL, LaBar KS, Beall SK, Brown VM, Haswell CC et al (2012) Amygdala volume changes in posttraumatic stress disorder in a large case-controlled veterans group. Arch Gen Psychiatry 69:1169–1178. doi:10.1001/archgenpsychiatry.2012.50

    PubMed Central  PubMed  Google Scholar 

  • Müller R, Abbet JP (1991) Changing trends in the consumption of legal and illegal drugs by 11–16-year-old adolescent pupils. Findings from a study conducted under the auspices of the WHO Europe. Swiss Professional Service for Alcohol Problems, Lausanne

  • Ochsner KN, Ray RD, Cooper JC, Robertson ER, Chopra S, Gabrieli JD et al (2004) For better or for worse: neural systems supporting the cognitive down- and up-regulation of negative emotion. Neuroimage 23:483–499. doi:10.1016/j.neuroimage.2004.06.030

    PubMed  Google Scholar 

  • Packard MG, Cahill L, McGaugh JL (1994) Amygdala modulation of hippocampal-dependent and caudate nucleus-dependent memory processes. Proc Natl Acad Sci USA 91:8477–8481

    PubMed Central  CAS  PubMed  Google Scholar 

  • Pezawas L, Meyer-Lindenberg A, Drabant EM, Verchinski BA, Munoz KE, Kolachana BS et al (2005) 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression. Nat Neurosci 8:828–834

    CAS  PubMed  Google Scholar 

  • Phelps EA (2004) Human emotion and memory: interactions of the amygdala and hippocampal complex. Curr Opin Neurobiol 14:198–202

    CAS  PubMed  Google Scholar 

  • Polanczyk G, Caspi A, Williams B, Price TS, Danese A, Sugden K et al (2009) Protective effect of CRHR1 gene variants on the development of adult depression following childhood maltreatment: replication and extension. Arch Gen Psychiatry 66:978–985

    PubMed Central  CAS  PubMed  Google Scholar 

  • Protopopescu X, Pan H, Tuescher O, Cloitre M, Goldstein M, Engelien W et al (2005) Differential time courses and specificity of amygdala activity in posttraumatic stress disorder subjects and normal control subjects. Biol Psychiatry 57:464–473. doi:10.1016/j.biopsych.2004.12.026

    PubMed  Google Scholar 

  • Rasch B, Papassotiropoulos A, de Quervain DF (2010a) Imaging genetics of cognitive functions: focus on episodic memory. Neuroimage 53:870–877. doi:10.1016/j.neuroimage.2010.01.001

    CAS  PubMed  Google Scholar 

  • Rasch B, Spalek K, Buholzer S, Luechinger R, Boesiger P, de Quervain DJ et al (2010b) Aversive stimuli lead to differential amygdala activation and connectivity patterns depending on catechol-O-methyltransferase Val158Met genotype. Neuroimage 52:1712–1719. doi:10.1016/j.neuroimage.2010.05.054

    CAS  PubMed  Google Scholar 

  • Rauch SL, Whalen PJ, Shin LM, McInerney SC, Macklin ML, Lasko NB et al (2000) Exaggerated amygdala response to masked facial stimuli in posttraumatic stress disorder: a functional MRI study. Biol Psychiatry 47:769–776 [Pii] S0006-3223(00)00828-3

    CAS  PubMed  Google Scholar 

  • Reul JM, de Kloet ER (1985) Two receptor systems for corticosterone in rat brain: microdistribution and differential occupation. Endocrinology 117:2505–2511

    CAS  PubMed  Google Scholar 

  • Ridout N, Noreen A, Johal J (2009) Memory for emotional faces in naturally occurring dysphoria and induced sadness. Behav Res Ther 47:851–860. doi:10.1016/j.brat.2009.06.013

    PubMed  Google Scholar 

  • Rolls ET, Grabenhorst F (2008) The orbitofrontal cortex and beyond: from affect to decision-making. Prog Neurobiol 86:216–244. doi:10.1016/j.pneurobio.2008.09.001

    PubMed  Google Scholar 

  • Root JC, Tuescher O, Cunningham-Bussel A, Pan H, Epstein J, Altemus M et al (2009) Frontolimbic function and cortisol reactivity in response to emotional stimuli. NeuroReport 20:429–434

    PubMed  Google Scholar 

  • Roozendaal B (2000) 1999 Curt P. Richter award. Glucocorticoids and the regulation of memory consolidation. Psychoneuroendocrinology 25:213–238 [pii] S030645309900058X

    CAS  PubMed  Google Scholar 

  • Roozendaal B, McGaugh JL (1997) Glucocorticoid receptor agonist and antagonist administration into the basolateral but not central amygdala modulates memory storage. Neurobiol Learn Mem 67:176–179. doi:10.1006/nlme.1996.3765

    CAS  PubMed  Google Scholar 

  • Roy A (1999) Childhood trauma and depression in alcoholics: relationship to hostility. J Affect Disord 56:215–218

    CAS  PubMed  Google Scholar 

  • Rutter M, Quinton D (1977) Psychiatric disorder—ecological factors and concepts of causation. In: McGurk M (ed) Ecological factors in human development. North Holland, Amsterdam, pp 173–187

    Google Scholar 

  • Sarchiapone M, Carli V, Cuomo C, Roy A (2007) Childhood trauma and suicide attempts in patients with unipolar depression. Depress Anxiety 24:268–272. doi:10.1002/da.20243

    PubMed  Google Scholar 

  • Scharf SH, Liebl C, Binder EB, Schmidt MV, Muller MB (2011) Expression and regulation of the FKBP5 gene in the adult mouse brain. PLoS One 6:e16883

    PubMed Central  CAS  PubMed  Google Scholar 

  • Schoenbaum G, Chiba AA, Gallagher M (2000) Changes in functional connectivity in orbitofrontal cortex and basolateral amygdala during learning and reversal training. J Neurosci 20:5179–5189 [pii] 20/13/5179

    CAS  PubMed  Google Scholar 

  • Sergerie K, Chochol C, Armony JL (2008) The role of the amygdala in emotional processing: a quantitative meta-analysis of functional neuroimaging studies. Neurosci Biobehav Rev 32:811–830

    PubMed  Google Scholar 

  • Siegle GJ, Thompson W, Carter CS, Steinhauer SR, Thase ME (2007) Increased amygdala and decreased dorsolateral prefrontal BOLD responses in unipolar depression: related and independent features. Biol Psychiatry 61:198–209. doi:10.1016/j.biopsych.2006.05.048

    PubMed  Google Scholar 

  • Taylor SE, Burklund LJ, Eisenberger NI, Lehman BJ, Hilmert CJ, Lieberman MD (2008) Neural bases of moderation of cortisol stress responses by psychosocial resources. J Pers Soc Psychol 95:197–211

    PubMed  Google Scholar 

  • Tebartz van Elst L, Woermann FG, Lemieux L, Trimble MR (1999) Amygdala enlargement in dysthymia—a volumetric study of patients with temporal lobe epilepsy. Biol Psychiatry 46:1614–1623 [pii] S0006-3223(99)00212-7

    CAS  PubMed  Google Scholar 

  • Torregrossa MM, Quinn JJ, Taylor JR (2008) Impulsivity, compulsivity, and habit: the role of orbitofrontal cortex revisited. Biol Psychiatry 63:253–255. doi:10.1016/j.biopsych.2007.11.014

    PubMed Central  PubMed  Google Scholar 

  • Tost H, Bilek E, Meyer-Lindenberg A (2012) Brain connectivity in psychiatric imaging genetics. Neuroimage 62:2250–2260. doi:10.1016/j.neuroimage.2011.11.007

    PubMed  Google Scholar 

  • Tottenham N, Hare TA, Quinn BT, McCarry TW, Nurse M, Gilhooly T et al (2010) Prolonged institutional rearing is associated with atypically large amygdala volume and difficulties in emotion regulation. Dev Sci 13:46–61

    PubMed Central  PubMed  Google Scholar 

  • Vaisvaser S, Lin T, Admon R, Podlipsky I, Greenman Y, Stern N et al (2013) Neural traces of stress: cortisol related sustained enhancement of amygdala-hippocampal functional connectivity. Front Hum Neurosci 7:313. doi:10.3389/fnhum.2013.00313

    PubMed Central  PubMed  Google Scholar 

  • van Eijndhoven P, van Wingen G, van Oijen K, Rijpkema M, Goraj B, Jan Verkes R et al (2009) Amygdala volume marks the acute state in the early course of depression. Biol Psychiatry 65:812–818. doi:10.1016/j.biopsych.2008.10.027

    PubMed  Google Scholar 

  • van Stegeren AH, Wolf OT, Everaerd W, Rombouts SA (2008) Interaction of endogenous cortisol and noradrenaline in the human amygdala. Prog Brain Res 167:263–268. doi:10.1016/S0079-6123(07)67020-4

    PubMed  Google Scholar 

  • Vassilopoulou K, Papathanasiou M, Michopoulos I, Boufidou F, Oulis P, Kelekis N et al (2013) A magnetic resonance imaging study of hippocampal, amygdala and subgenual prefrontal cortex volumes in major depression subtypes: melancholic versus psychotic depression. J Affect Disord 146:197–204. doi:10.1016/j.jad.2012.09.003

    PubMed  Google Scholar 

  • Veer IM, Oei NY, Spinhoven P, van Buchem MA, Elzinga BM, Rombouts SA (2012) Endogenous cortisol is associated with functional connectivity between the amygdala and medial prefrontal cortex. Psychoneuroendocrinology 37:1039–1047. doi:10.1016/j.psyneuen.2011.12.001

    CAS  PubMed  Google Scholar 

  • von Gunten A, Fox NC, Cipolotti L, Ron MA (2000) A volumetric study of hippocampus and amygdala in depressed patients with subjective memory problems. J Neuropsychiatry Clin Neurosci 12:493–498

    Google Scholar 

  • Watkins PC, Mathews A, Williamson DA, Fuller RD (1992) Mood-congruent memory in depression: emotional priming or elaboration? J Abnorm Psychol 101:581–586

    CAS  PubMed  Google Scholar 

  • White MG, Bogdan R, Fisher PM, Munoz KE, Williamson DE, Hariri AR (2012) FKBP5 and emotional neglect interact to predict individual differences in amygdala reactivity. Genes Brain Behav 11:869–878. doi:10.1111/j.1601-183X.2012.00837.x

    CAS  PubMed  Google Scholar 

  • Wingenfeld K, Spitzer C, Mensebach C, Grabe HJ, Hill A, Gast U et al (2010) The German version of the Childhood Trauma Questionnaire (CTQ): preliminary psychometric properties. Psychother Psychosom Med Psychol 60:442–450

    PubMed  Google Scholar 

  • Wittchen HU, Zaudig M, Fydrich T (1997) Structured clinical interview for DSM-IV Axis I and II—SCID. Hogrefe, Göttingen

    Google Scholar 

  • Wittchen HU, Jacobi F, Rehm J, Gustavsson A, Svensson M, Jonsson B et al (2011) The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur Neuropsychopharmacology 21:655–679

    CAS  Google Scholar 

  • Wochnik GM, Ruegg J, Abel GA, Schmidt U, Holsboer F, Rein T (2005) FK506-binding proteins 51 and 52 differentially regulate dynein interaction and nuclear translocation of the glucocorticoid receptor in mammalian cells. J Biol Chem 280:4609–4616. doi:10.1074/jbc.M407498200

    CAS  PubMed  Google Scholar 

  • Zobel A, Schuhmacher A, Jessen F, Hofels S, von WO, Metten M et al (2010) DNA sequence variants of the FKBP5 gene are associated with unipolar depression. Int J Neuropsychopharmacol 13:649–660. doi:10.1017/S1461145709991155

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the German Research Foundation to ML, DB, AML, and TB. The authors thank Sibylle Heinzel, Elisabeth Reichert, Erika Hohm, Katrin Zohsel, Anna Becker, Angelika Bocklage, Andrea Len, Daniel Megally and Elise Jezycki for conducting and supporting the assessments. In addition we thank Martin Gerchen for helpful comments on the results.

Conflict of interest

TB served in an advisory or consultancy role for Hexal Pharma, Lilly, Medice, Novartis, Otsuka, Oxford outcomes, PCM scientific, Shire and Viforpharma. He received conference attendance support and conference support or received speaker’s fee by Lilly, Medice, Novartis and Shire. He is/has been involved in clinical trials conducted by Lilly, Shire & Viforpharma. AML receives consultant fees and travel expenses from AstraZeneca, Hoffmann-La Roche, Lundbeck Foundation, speaker’s fees from Pfizer Pharma, Lilly Deutschland, Glaxo SmithKline, Janssen Cilag, Bristol-Myers Squibb, Lundbeck and AstraZeneca. All other authors declare that they have no biomedical financial interest or potential conflicts of interest. The present work is unrelated to the above grants and relationships.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Manfred Laucht.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Holz, N.E., Buchmann, A.F., Boecker, R. et al. Role of FKBP5 in emotion processing: results on amygdala activity, connectivity and volume. Brain Struct Funct 220, 1355–1368 (2015). https://doi.org/10.1007/s00429-014-0729-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00429-014-0729-5

Keywords

Navigation