Advertisement

Deficient Amygdala Habituation to Threatening Stimuli in Borderline Personality Disorder Relates to Adverse Childhood Experiences

      Abstract

      Background

      Heightened amygdala response to threatening cues has been repeatedly observed in borderline personality disorder (BPD). A previous report linked hyperactivation to deficient amygdala habituation to repeated stimuli, but the biological underpinnings are incompletely understood.

      Methods

      We examined a sample of 120 patients with BPD and 115 healthy control subjects with a well-established functional magnetic resonance imaging emotional face processing task to replicate the previously reported amygdala habituation deficit in BPD and probed this neural phenotype for associations with symptom severity and early social risk exposure.

      Results

      Our results confirm a significant reduction in amygdala habituation to repeated negative stimuli in BPD (pFWE = .015, peak-level familywise error [FWE] corrected for region of interest). Post hoc comparison and regression analysis did not suggest a role for BPD clinical state (pFWE > .56) or symptom severity (pFWE > .45) for this phenotype. Furthermore, deficient amygdala habituation was significantly related to increased exposure to adverse childhood experiences (pFWE = .013, region of interest corrected).

      Conclusions

      Our data replicate a prior report on deficient amygdala habituation in BPD and link this neural phenotype to early adversity, a well-established social environmental risk factor for emotion dysregulation and psychiatric illness.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Schmahl C.
        • Herpertz S.C.
        • Bertsch K.
        • Ende G.
        • Flor H.
        • Kirsch P.
        • et al.
        Mechanisms of disturbed emotion processing and social interaction in borderline personality disorder: State of knowledge and research agenda of the German Clinical Research Unit.
        Borderline Personal Disord Emot Dysregul. 2014; 1: 12
        • Tomko R.L.
        • Trull T.J.
        • Wood P.K.
        • Sher K.J.
        Characteristics of borderline personality disorder in a community sample: Comorbidity, treatment utilization, and general functioning.
        J Person Disord. 2014; 28: 734-750
        • Tragesser S.L.
        • Solhan M.
        • Schwartz-Mette R.
        • Trull T.J.
        The role of affective instability and impulsivity in predicting future BPD features.
        J Person Disord. 2007; 21: 603-614
        • Linehan M.M.
        • Kehrer C.A.
        Borderline personality disorder.
        in: Barlow D.H. Clinical Handbook of Psychological Disorders: A Step-By-Step Treatment Manual. 2 ed. Guilford Press, New York1993: 396-441
        • Leichsenring F.
        • Leibing E.
        • Kruse J.
        • New A.S.
        • Leweke F.
        Borderline personality disorder.
        Lancet. 2011; 377: 74-84
        • Torgersen S.
        Genetics of patients with borderline personality disorder.
        Psychiatr Clin North Am. 2000; 23: 1-9
        • Herpertz S.C.
        • Dietrich T.M.
        • Wenning B.
        • Krings T.
        • Erberich S.G.
        • Willmes K.
        • et al.
        Evidence of abnormal amygdala functioning in borderline personality disorder: A functional MRI study.
        Biol Psychiatry. 2001; 50: 292-298
        • Donegan N.H.
        • Sanislow C.A.
        • Blumberg H.P.
        • Fulbright R.K.
        • Lacadie C.
        • Skudlarski P.
        • et al.
        Amygdala hyperreactivity in borderline personality disorder: Implications for emotional dysregulation.
        Biol Psychiatry. 2003; 54: 1284-1293
        • Minzenberg M.J.
        • Fan J.
        • New A.S.
        • Tang C.Y.
        • Siever L.J.
        Fronto-limbic dysfunction in response to facial emotion in borderline personality disorder: An event-related fMRI study.
        Psychiatry Res. 2007; 155: 231-243
        • Schulze L.
        • Schmahl C.
        • Niedtfeld I.
        Neural correlates of disturbed emotion processing in borderline personality disorder: A multimodal meta-analysis.
        Biol Psychiatry. 2016; 79: 97-106
        • Koenigsberg H.W.
        • Siever L.J.
        • Lee H.
        • Pizzarello S.
        • New A.S.
        • Goodman M.
        • et al.
        Neural correlates of emotion processing in borderline personality disorder.
        Psychiatry Res. 2009; 172: 192-199
        • Bordi F.
        • LeDoux J.
        Sensory tuning beyond the sensory system: An initial analysis of auditory response properties of neurons in the lateral amygdaloid nucleus and overlying areas of the striatum.
        J Neurosci. 1992; 12: 2493-2503
        • Breiter H.C.
        • Etcoff N.L.
        • Whalen P.J.
        • Kennedy W.A.
        • Rauch S.L.
        • Buckner R.L.
        • et al.
        Response and habituation of the human amygdala during visual processing of facial expression.
        Neuron. 1996; 17: 875-887
        • Phillips M.L.
        • Medford N.
        • Young A.W.
        • Williams L.
        • Williams S.C.
        • Bullmore E.T.
        • et al.
        Time courses of left and right amygdalar responses to fearful facial expressions.
        Hum Brain Mapp. 2001; 12: 193-202
        • Rankin C.H.
        • Abrams T.
        • Barry R.J.
        • Bhatnagar S.
        • Clayton D.F.
        • Colombo J.
        • et al.
        Habituation revisited: An updated and revised description of the behavioral characteristics of habituation.
        Neurobiol Learn Mem. 2009; 92: 135-138
        • Plichta M.M.
        • Grimm O.
        • Morgen K.
        • Mier D.
        • Sauer C.
        • Haddad L.
        • et al.
        Amygdala habituation: Areliable fMRI phenotype.
        NeuroImage. 2014; 103: 383-390
        • Plichta M.M.
        • Schwarz A.J.
        • Grimm O.
        • Morgen K.
        • Mier D.
        • Haddad L.
        • et al.
        Test-retest reliability of evoked BOLD signals from a cognitive-emotive fMRI test battery.
        NeuroImage. 2012; 60: 1746-1758
        • Gee D.G.
        • McEwen S.C.
        • Forsyth J.K.
        • Haut K.M.
        • Bearden C.E.
        • Addington J.
        • et al.
        Reliability of an fMRI paradigm for emotional processing in a multisite longitudinal study.
        Hum Brain Mapp. 2015; 36: 2558-2579
        • Hazlett E.A.
        • Zhang J.
        • New A.S.
        • Zelmanova Y.
        • Goldstein K.E.
        • Haznedar M.M.
        • et al.
        Potentiated amygdala response to repeated emotional pictures in borderline personality disorder.
        Biol Psychiatry. 2012; 72: 448-456
        • Goodman M.
        • Carpenter D.
        • Tang C.Y.
        • Goldstein K.E.
        • Avedon J.
        • Fernandez N.
        • et al.
        Dialectical behavior therapy alters emotion regulation and amygdala activity in patients with borderline personality disorder.
        J Psychiatr Res. 2014; 57: 108-116
        • Lonsdorf T.B.
        • Golkar A.
        • Lindstom K.M.
        • Fransson P.
        • Schalling M.
        • Ohman A.
        • et al.
        5-HTTLPR and COMTval158met genotype gate amygdala reactivity and habituation.
        Biol Psychol. 2011; 87: 106-112
        • Perez-Rodriguez M.M.
        • New A.S.
        • Goldstein K.E.
        • Rosell D.
        • Yuan Q.
        • Zhou Z.
        • et al.
        Brain-derived neurotrophic factor Val66Met genotype modulates amygdala habituation.
        Psychiatry Res Neuroimag. 2017; 263: 85-92
        • Hariri A.R.
        • Mattay V.S.
        • Tessitore A.
        • Kolachana B.
        • Fera F.
        • Goldman D.
        • et al.
        Serotonin transporter genetic variation and the response of the human amygdala.
        Science. 2002; 297: 400-403
        • Wittchen H.-U.
        • Wunderlich U.
        • Gruschwitz S.
        • Zaudig M.
        SKID I. Strukturiertes Klinisches Interview für DSM-IV. Achse I: Psychische Störungen. Interviewheft und Beurteilungsheft. Eine deutschsprachige, erweiterte Bearb. d. amerikanischen Originalversion des SKID I.
        Goettingen, Hogrefe-Verlag1997
        • Loranger A.W.
        IPDE: International Personality Disorder Examination: DSM-IV and ICD-10 Interviews.
        PARS Psychological Assessment Resources, Lutz, FL1999
        • Raven J.
        • Raven J.C.
        • Court J.H.
        Raven Manual: Section 4, Advanced Progressive Matrices.
        Oxford Psychologists Press, Oxford, UK1998
        • Bernstein D.P.
        • Fink L.
        Childhood Trauma Questionnaire: A Retrospective Self-Report: Manual.
        Harcourt Brace & Co, San Antonio, TX1998
        • Bohus M.
        • Limberger M.F.
        • Frank U.
        • Chapman A.L.
        • Kuhler T.
        • Stieglitz R.D.
        Psychometric properties of the Borderline Symptom List (BSL).
        Psychopathology. 2007; 40: 126-132
        • Freyberger H.J.
        • Spitzer C.
        • Stieglitz R.D.
        Fragebogen zu Dissoziative Symptomen (FDS). German adaptation of the Dissociative Experience Scale (DES).
        Huber, Bern1986
        • American Psychiatric Association
        Diagnostic and Statistical Manual Of Mental Disorders, 4th ed, text revision.
        American Psychiatric Publishing, Washington, DC2000
        • Beck A.T.
        BDI-II, Beck Depression Inventory: Manual.
        2nd ed. Psychological Corp., San Antonio, TX1996
        • Patton J.H.
        • Stanford M.S.
        • Barratt E.S.
        Factor structure of the Barratt impulsiveness scale.
        J Clin Psychol. 1995; 51: 768-774
        • Bradley M.M.
        • Lang P.J.
        Measuring emotion: the self-assessment manikin and the semantic differential.
        J Behav Ther Exp Psychiatry. 1994; 25: 49-59
        • Ekman P.
        • Friesen W.V.
        Measuring facial movement.
        Environment Psychol Nonverbal Behav. 1976; 1: 56-75
        • Wiggins J.L.
        • Swartz J.R.
        • Martin D.M.
        • Lord C.
        • Monk C.S.
        Serotonin transporter genotype impacts amygdala habituation in youth with autism spectrum disorders.
        Soc Cogn Affect Neurosci. 2014; 9: 832-838
        • Tzourio-Mazoyer N.
        • Landeau B.
        • Papathanassiou D.
        • Crivello F.
        • Etard O.
        • Delcroix N.
        • et al.
        Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain.
        NeuroImage. 2002; 15: 273-289
        • Wright C.I.
        • Fischer H.
        • Whalen P.J.
        • McInerney S.C.
        • Shin L.M.
        • Rauch S.L.
        Differential prefrontal cortex and amygdala habituation to repeatedly presented emotional stimuli.
        Neuroreport. 2001; 12: 379-383
        • Baas D.
        • Aleman A.
        • Kahn R.S.
        Lateralization of amygdala activation: a systematic review of functional neuroimaging studies.
        Brain Res Brain Res Rev. 2004; 45: 96-103
        • Liebschutz J.M.
        • Buchanan-Howland K.
        • Chen C.A.
        • Frank D.A.
        • Richardson M.A.
        • Heeren T.C.
        • et al.
        Childhood Trauma Questionnaire (CTQ) correlations with prospective violence assessment in a longitudinal cohort.
        Psychol Assess. 2018; 30: 841-845
        • Glaesmer H.
        • Schulz A.
        • Hauser W.
        • Freyberger H.J.
        • Brahler E.
        • Grabe H.J.
        [The childhood trauma screener (CTS) - development and validation of cut-off-scores for classificatory diagnostics].
        Psychiatr Praxis. 2013; 40: 220-226
        • Pieritz K.
        • Rief W.
        • Euteneuer F.
        Childhood adversities and laboratory pain perception.
        Neuropsychiatr Dis Treat. 2015; 11: 2109-2116
        • Fisher P.M.
        • Meltzer C.C.
        • Price J.C.
        • Coleman R.L.
        • Ziolko S.K.
        • Becker C.
        • et al.
        Medial prefrontal cortex 5-HT(2A) density is correlated with amygdala reactivity, response habituation, and functional coupling.
        Cereb Cortex. 2009; 19: 2499-2507
        • Kleinhans N.M.
        • Johnson L.C.
        • Richards T.
        • Mahurin R.
        • Greenson J.
        • Dawson G.
        • et al.
        Reduced neural habituation in the amygdala and social impairments in autism spectrum disorders.
        Am J Psychiatry. 2009; 166: 467-475
        • Kleinhans N.M.
        • Richards T.
        • Greenson J.
        • Dawson G.
        • Aylward E.
        Altered dynamics of the fMRI response to faces in individuals with autism.
        J Autism Dev Disord. 2016; 46: 232-241
        • Blackford J.U.
        • Allen A.H.
        • Cowan R.L.
        • Avery S.N.
        Amygdala and hippocampus fail to habituate to faces in individuals with an inhibited temperament.
        Soc Cogn Affect Neurosci. 2012; 8: 143-150
        • Witt S.H.
        • Streit F.
        • Jungkunz M.
        • Frank J.
        • Awasthi S.
        • Reinbold C.S.
        • et al.
        Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia.
        Transl Psychiatry. 2017; 7: e1155
        • Denny B.T.
        • Fan J.
        • Fels S.
        • Galitzer H.
        • Schiller D.
        • Koenigsberg H.W.
        Sensitization of the neural salience network to repeated emotional stimuli following initial habituation in patients with borderline personality disorder.
        Am J Psychiatry. 2018; 175: 657-664

      Linked Article