The Neuropsychological Mechanisms of Treatment of Bipolar Disorder and Borderline Personality Disorder: Activation Likelihood Estimation Meta-Analysis of Brain Imaging Research
Objective: To explore the alteration of brain regions after treatments for bipolar disorder (BD) and borderline personality disorder (BPD) in order to discover the underlying neural mechanisms of therapies.
Data Sources: An electronic search of the PubMed, Embase, Cochrane Library, and Web of Science databases from inception until June 2021 was conducted.
Study Selection: Articles reporting the results of changes in brain activation after treatment, to assess the effects of therapy relative to a before-treatment condition, were included. A total of 1,592 records were retrieved, with 34 studies ultimately included.
Data Extraction: Activation coordinates were extracted from each study. We used activation likelihood estimation meta-analysis to evaluate the similarities and differences in the activation of different brain regions in patients with BD and BPD after treatment with psychotherapy and drug therapy.
Results: Most brain regions with abnormal activation were improved after treatments for BD and BPD. The brain activity changes produced by psychotherapy were mostly in the frontal areas, while drug therapy primarily impacted the limbic areas. In BD, treatments were associated with activation alterations in the inferior frontal gyrus, superior temporal gyrus, and cingulate gyrus, while in BPD, treatments were associated with activation alterations in the supramarginal gyrus, middle frontal gyrus, and parahippocampal gyrus.
Conclusions: These results suggest that drug therapy might have a bottom-up effect, while psychotherapy might have a top-down effect. This study may contribute to the clinical prediction of treatment efficacy in BD and BPD and to the identification of more accurate neuroimaging biomarkers for treatment of the two disorders.
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Benazzi F. Bipolar II disorder: epidemiology, diagnosis and management. CNS Drugs. 2007;21(9):727–740. PubMedCrossRef
Teh WL, Abdin E, Vaingankar J, et al. Prevalence and correlates of bipolar spectrum disorders in Singapore: results from the 2016 Singapore Mental Health Study (SMHS 2016). J Affect Disord. 2020;274:339–346. PubMedCrossRef
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fifth Edition. American Psychiatric Publishing; 2013.
Grant BF, Chou SP, Goldstein RB, et al. Prevalence, correlates, disability, and comorbidity of DSM-IV borderline personality disorder: results from the Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions. J Clin Psychiatry. 2008;69(4):533–545. PubMedCrossRef
Chanen A, Sharp C, Hoffman P; Global Alliance for Prevention and Early Intervention for Borderline Personality Disorder. Prevention and early intervention for borderline personality disorder: a novel public health priority. World Psychiatry. 2017;16(2):215–216. PubMedCrossRef
Ghaemi SN, Barroilhet S. Confusing borderline personality with severe bipolar illness. Acta Psychiatr Scand. 2015;132(4):281–282. PubMedCrossRef
Agius M, Lee J, Gardner J, et al. Bipolar II disorder and borderline personality disorder - co-morbidity or spectrum? Psychiatr Danub. 2012;24(suppl 1):S197–S201. PubMed
Vieta E, Suppes T. Bipolar II disorder: arguments for and against a distinct diagnostic entity. Bipolar Disord. 2008;10(1 Pt 2):163–178. PubMedCrossRef
Fornaro M, Orsolini L, Marini S, et al. The prevalence and predictors of bipolar and borderline personality disorders comorbidity: Systematic review and meta-analysis. J Affect Disord. 2016;195:105–118. PubMedCrossRef
Henry C, Mitropoulou V, New AS, et al. Affective instability and impulsivity in borderline personality and bipolar II disorders: similarities and differences. J Psychiatr Res. 2001;35(6):307–312. PubMedCrossRef
Zimmerman M, Morgan TA. Problematic boundaries in the diagnosis of bipolar disorder: the interface with borderline personality disorder. Curr Psychiatry Rep. 2013;15(12):422. PubMedCrossRef
Paris J, Black DW. Borderline personality disorder and bipolar disorder: what is the difference and why does it matter? J Nerv Ment Dis. 2015;203(1):3–7. PubMedCrossRef
Oud M, Mayo-Wilson E, Braidwood R, et al. Psychological interventions for adults with bipolar disorder: systematic review and meta-analysis. Br J Psychiatry. 2016;208(3):213–222. PubMedCrossRef
Chiang KJ, Tsai JC, Liu D, et al. Efficacy of cognitive-behavioral therapy in patients with bipolar disorder: a meta-analysis of randomized controlled trials. PLoS One. 2017;12(5):e0176849. PubMedCrossRef
Szentagotai A, David D. The efficacy of cognitive-behavioral therapy in bipolar disorder: a quantitative meta-analysis. J Clin Psychiatry. 2010;71(1):66–72. PubMedCrossRef
Bailly D. Pharmacological treatment of bipolar disorder in children and adolescents. Encephale. 2017;43(3):254–258. PubMedCrossRef
Tamayo JM, Zarate CA Jr, Vieta E, et al. Level of response and safety of pharmacological monotherapy in the treatment of acute bipolar I disorder phases: a systematic review and meta-analysis. Int J Neuropsychopharmacol. 2010;13(6):813–832. PubMedCrossRef
Zimmerman M, Morgan TA. The relationship between borderline personality disorder and bipolar disorder. Dialogues Clin Neurosci. 2013;15(2):155–169. PubMedCrossRef
Asherson P, Young AH, Eich-Höchli D, et al. Differential diagnosis, comorbidity, and treatment of attention-deficit/hyperactivity disorder in relation to bipolar disorder or borderline personality disorder in adults. Curr Med Res Opin. 2014;30(8):1657–1672. PubMedCrossRef
Dadomo H, Salvato G, Lapomarda G, et al. Structural features predict sexual trauma and interpersonal problems in borderline personality disorder but not in controls: a multi-voxel pattern analysis. Front Hum Neurosci. 2022;16:773593. PubMedCrossRef
Grecucci A, Lapomarda G, Messina I, et al. Structural features related to affective instability correctly classify patients with borderline personality disorder. a supervised machine learning approach. Front Psychiatry. 2022;13:804440. PubMedCrossRef
Ding JB, Hu K. Structural MRI brain alterations in borderline personality disorder and bipolar disorder. Cureus. 2021;13(7):e16425. PubMedCrossRef
Donegan NH, Sanislow CA, Blumberg HP, et al. Amygdala hyperreactivity in borderline personality disorder: implications for emotional dysregulation. Biol Psychiatry. 2003;54(11):1284–1293. PubMedCrossRef
Lapomarda G, Grecucci A, Messina I, et al. Common and different gray and white matter alterations in bipolar and borderline personality disorder: a source-based morphometry study. Brain Res. 2021;1762:147401. PubMedCrossRef
Davies G, Hayward M, Evans S, et al. A systematic review of structural MRI investigations within borderline personality disorder: identification of key psychological variables of interest going forward. Psychiatry Res. 2020;286:112864. PubMedCrossRef
Schulze L, Schmahl C, Niedtfeld I. Neural correlates of disturbed emotion processing in borderline personality disorder: a multimodal meta-analysis. Biol Psychiatry. 2016;79(2):97–106. PubMedCrossRef
Lapomarda G, Pappaianni E, Siugzdaite R, et al. Out of control: an altered parieto-occipital-cerebellar network for impulsivity in bipolar disorder. Behav Brain Res. 2021;406:113228. PubMedCrossRef
Diler RS, Segreti AM, Ladouceur CD, et al. Neural correlates of treatment in adolescents with bipolar depression during response inhibition. J Child Adolesc Psychopharmacol. 2013a;23(3):214–221. PubMedCrossRef
Favre P, Baciu M, Pichat C, et al. Modulation of fronto-limbic activity by the psychoeducation in euthymic bipolar patients: a functional MRI study. Psychiatry Res. 2013;214(3):285–295. PubMedCrossRef
Bertsch K, Gamer M, Schmidt B, et al. Oxytocin and reduction of social threat hypersensitivity in women with borderline personality disorder. Am J Psychiatry. 2013;170(10):1169–1177. PubMedCrossRef
Carmona I Farrés C, Elices M, Soler J, et al. Effects of mindfulness training on the default mode network in borderline personality disorder. Clin Psychol Psychother. 2019;26(5):562–571. PubMedCrossRef
Lischke A, Herpertz SC, Berger C, et al. Divergent effects of oxytocin on (para-)limbic reactivity to emotional and neutral scenes in females with and without borderline personality disorder. Soc Cogn Affect Neurosci. 2017;12(11):1783–1792. PubMedCrossRef
Moher D, Liberati A, Tetzlaff J, et al; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097. PubMedCrossRef
Eickhoff SB, Laird AR, Grefkes C, et al. Coordinate-based activation likelihood estimation meta-analysis of neuroimaging data: a random-effects approach based on empirical estimates of spatial uncertainty. Hum Brain Mapp. 2009;30(9):2907–2926. PubMedCrossRef
Laird AR, Eickhoff SB, Fox PM, et al. The BrainMap strategy for standardization, sharing, and meta-analysis of neuroimaging data. BMC Res Notes. 2011;4(1):349. PubMedCrossRef
Lancaster JL, Tordesillas-Gutiérrez D, Martinez M, et al. Bias between MNI and Talairach coordinates analyzed using the ICBM-152 brain template. Hum Brain Mapp. 2007;28(11):1194–1205. PubMedCrossRef
Eickhoff SB, Nichols TE, Laird AR, et al. Behavior, sensitivity, and power of activation likelihood estimation characterized by massive empirical simulation. Neuroimage. 2016;137:70–85. PubMedCrossRef
Turkeltaub PE, Eickhoff SB, Laird AR, et al. Minimizing within-experiment and within-group effects in activation likelihood estimation meta-analyses. Hum Brain Mapp. 2012;33(1):1–13. PubMedCrossRef
Lancaster JL, Cykowski MD, McKay DR, et al. Anatomical global spatial normalization. Neuroinformatics. 2010;8(3):171–182. PubMedCrossRef
Deckersbach T, Peters AT, Shea C, et al. Memory performance predicts response to psychotherapy for depression in bipolar disorder: a pilot randomized controlled trial with exploratory functional magnetic resonance imaging. J Affect Disord. 2018;229:342–350. PubMedCrossRef
Ives-Deliperi VL, Howells F, Stein DJ, et al. The effects of mindfulness-based cognitive therapy in patients with bipolar disorder: a controlled functional MRI investigation. J Affect Disord. 2013;150(3):1152–1157. PubMedCrossRef
Meusel L-AC, Hall GB, Fougere P, et al. Neural correlates of cognitive remediation in patients with mood disorders. Psychiatry Res. 2013;214(2):142–152. PubMedCrossRef
Venza EE, Chapman SB, Aslan S, et al. Enhancing executive function and neural health in bipolar disorder through reasoning training. Front Psychol. 2016;7:1676–1686. PubMedCrossRef
Diler RS, Ladouceur CD, Segreti A, et al. Neural correlates of treatment response in depressed bipolar adolescents during emotion processing. Brain Imaging Behav. 2013;7(2):227–235. PubMedCrossRef
Garrett AS, Chang KD, Singh MK, et al. Neural changes in youth at high risk for bipolar disorder undergoing family-focused therapy or psychoeducation. Bipolar Disord. 2021;23(6):604–614. PubMedCrossRef
Haldane M, Jogia J, Cobb A, et al. Changes in brain activation during working memory and facial recognition tasks in patients with bipolar disorder with lamotrigine monotherapy. Eur Neuropsychopharmacol. 2008;18(1):48–54. PubMedCrossRef
Jogia J, Haldane M, Cobb A, et al. Pilot investigation of the changes in cortical activation during facial affect recognition with lamotrigine monotherapy in bipolar disorder. Br J Psychiatry. 2008;192(3):197–201. PubMedCrossRef
Marchand WR, Lee JN, Thatcher J, et al. A preliminary longitudinal fMRI study of frontal-subcortical circuits in bipolar disorder using a paced motor activation paradigm. J Affect Disord. 2007;103(1–3):237–241. PubMedCrossRef
Passarotti AM, Sweeney JA, Pavuluri MN. Fronto-limbic dysfunction in mania pre-treatment and persistent amygdala over-activity post-treatment in pediatric bipolar disorder. Psychopharmacology (Berl). 2011;216(4):485–499. PubMedCrossRef
Pavuluri MN, Passarotti AM, Fitzgerald JM, et al. Risperidone and divalproex differentially engage the fronto-striato-temporal circuitry in pediatric mania: a pharmacological functional magnetic resonance imaging study. J Am Acad Child Adolesc Psychiatry. 2012b;51(2):157–170.e5. PubMedCrossRef
Pavuluri MN, Passarotti AM, Lu LH, et al. Double-blind randomized trial of risperidone versus divalproex in pediatric bipolar disorder: fMRI outcomes. Psychiatry Res. 2011;193(1):28–37. PubMedCrossRef
Pavuluri MN, Passarotti AM, Parnes SA, et al. A pharmacological functional magnetic resonance imaging study probing the interface of cognitive and emotional brain systems in pediatric bipolar disorder. J Child Adolesc Psychopharmacol. 2010;20(5):395–406. PubMedCrossRef
Yang H, Lu LH, Wu M, et al. Time course of recovery showing initial prefrontal cortex changes at 16 weeks, extending to subcortical changes by 3 years in pediatric bipolar disorder. J Affect Disord. 2013;150(2):571–577. PubMedCrossRef
Miskowiak KW, Vinberg M, Glerup L, et al. Neural correlates of improved executive function following erythropoietin treatment in mood disorders. Psychol Med. 2016;46(8):1679–1691. PubMedCrossRef
Miskowiak KW, Petersen NA, Harmer CJ, et al. Neural correlates of improved recognition of happy faces after erythropoietin treatment in bipolar disorder. Acta Psychiatr Scand. 2018;138(4):336–347. PubMedCrossRef
Chang K, DelBello M, Garrett A, et al. Neurofunctional correlates of response to quetiapine in adolescents with bipolar depression. J Child Adolesc Psychopharmacol. 2018;28(6):379–386. PubMedCrossRef
Strakowski SM, Fleck DE, Welge J, et al. fMRI brain activation changes following treatment of a first bipolar manic episode. Bipolar Disord. 2016;18(6):490–501. PubMedCrossRef
Miskowiak KW, Macoveanu J, Vinberg M, et al. Effects of erythropoietin on memory-relevant neurocircuitry activity and recall in mood disorders. Acta Psychiatr Scand. 2016;134(3):249–259. PubMedCrossRef
Dandash O, Yücel M, Daglas R, et al. Differential effect of quetiapine and lithium on functional connectivity of the striatum in first episode mania. Transl Psychiatry. 2018;8(1):59. PubMedCrossRef
Driessen M, Wingenfeld K, Rullkoetter N, et al. One-year functional magnetic resonance imaging follow-up study of neural activation during the recall of unresolved negative life events in borderline personality disorder. Psychol Med. 2009;39(3):507–516. PubMedCrossRef
Niedtfeld I, Schmitt R, Winter D, et al. Pain-mediated affect regulation is reduced after dialectical behavior therapy in borderline personality disorder: a longitudinal fMRI study. Soc Cogn Affect Neurosci. 2017;12(5):739–747. PubMedCrossRef
Paret C, Kluetsch R, Zaehringer J, et al. Alterations of amygdala-prefrontal connectivity with real-time fMRI neurofeedback in BPD patients. Soc Cogn Affect Neurosci. 2016;11(6):952–960. PubMedCrossRef
Perez DL, Vago DR, Pan H, et al. Frontolimbic neural circuit changes in emotional processing and inhibitory control associated with clinical improvement following transference-focused psychotherapy in borderline personality disorder. Psychiatry Clin Neurosci. 2016;70(1):51–61. PubMedCrossRef
Schmitt R, Winter D, Niedtfeld I, et al. Effects of psychotherapy on neuronal correlates of reappraisal in female patients with borderline personality disorder. Biol Psychiatry Cogn Neurosci Neuroimaging. 2016;1(6):548–557. PubMedCrossRef
Schnell K, Herpertz SC. Effects of dialectic-behavioral-therapy on the neural correlates of affective hyperarousal in borderline personality disorder. J Psychiatr Res. 2007;41(10):837–847. PubMedCrossRef
Winter D, Niedtfeld I, Schmitt R, et al. Neural correlates of distraction in borderline personality disorder before and after dialectical behavior therapy. Eur Arch Psychiatry Clin Neurosci. 2017;267(1):51–62. PubMedCrossRef
Metz S, Fleischer J, Gärnter M, et al. Effects of hydrocortisone on autobiographical memory retrieval in patients with posttraumatic stress disorder and borderline personality disorder: the role of childhood trauma. Neuropsychopharmacology. 2019;44(12):2038–2044. PubMedCrossRef
Pavuluri MN, Ellis JA, Wegbreit E, et al. Pharmacotherapy impacts functional connectivity among affective circuits during response inhibition in pediatric mania. Behav Brain Res. 2012;226(2):493–503. PubMedCrossRef
Zovetti N, Rossetti MG, Perlini C, et al. Default mode network activity in bipolar disorder. Epidemiol Psychiatr Sci. 2020;29:e166. PubMedCrossRef
Visintin E, De Panfilis C, Amore M, et al. Mapping the brain correlates of borderline personality disorder: a functional neuroimaging meta-analysis of resting state studies. J Affect Disord. 2016;204:262–269. PubMedCrossRef
Leech R, Kamourieh S, Beckmann CF, et al. Fractionating the default mode network: distinct contributions of the ventral and dorsal posterior cingulate cortex to cognitive control. J Neurosci. 2011;31(9):3217–3224. PubMedCrossRef
Bateman AW, Gunderson J, Mulder R. Treatment of personality disorder. Lancet. 2015;385(9969):735–743. PubMedCrossRef
Aminoff EM, Kveraga K, Bar M. The role of the parahippocampal cortex in cognition. Trends Cogn Sci. 2013;17(8):379–390. PubMedCrossRef
Ochsner KN, Ray RR, Hughes B, et al. Bottom-up and top-down processes in emotion generation: common and distinct neural mechanisms. Psychol Sci. 2009;20(11):1322–1331. PubMedCrossRef
Malhi GS, Tanious M, Fritz K, et al. Differential engagement of the fronto-limbic network during emotion processing distinguishes bipolar and borderline personality disorder. Mol Psychiatry. 2013;18(12):1247–1248. PubMedCrossRef
Etkin A, Egner T, Peraza DM, et al. Resolving emotional conflict: a role for the rostral anterior cingulate cortex in modulating activity in the amygdala. Neuron. 2006;51(6):871–882. PubMedCrossRef
Flasbeck V, Enzi B, Brüne M. Enhanced processing of painful emotions in patients with borderline personality disorder: a functional magnetic resonance imaging study. Front Psychiatry. 2019;10:357. PubMedCrossRef
Carter CS, Braver TS, Barch DM, et al. Anterior cingulate cortex, error detection, and the online monitoring of performance. Science. 1998;280(5364):747–749. PubMedCrossRef
Townsend J, Altshuler LL. Emotion processing and regulation in bipolar disorder: a review. Bipolar Disord. 2012;14(4):326–339. PubMedCrossRef
Völlm BA, Taylor AN, Richardson P, et al. Neuronal correlates of theory of mind and empathy: a functional magnetic resonance imaging study in a nonverbal task. Neuroimage. 2006;29(1):90–98. PubMedCrossRef
Fransson P, Marrelec G. The precuneus/posterior cingulate cortex plays a pivotal role in the default mode network: evidence from a partial correlation network analysis. Neuroimage. 2008;42(3):1178–1184. PubMedCrossRef
O’Neill A, D’Souza A, Samson AC, et al. Dysregulation between emotion and theory of mind networks in borderline personality disorder. Psychiatry Res. 2015;231(1):25–32. PubMedCrossRef
Herpertz SC, Dietrich TM, Wenning B, et al. Evidence of abnormal amygdala functioning in borderline personality disorder: a functional MRI study. Biol Psychiatry. 2001;50(4):292–298. PubMedCrossRef
Massó Rodriguez A, Hogg B, Gardoki-Souto I, et al. Clinical features, neuropsychology and neuroimaging in bipolar and borderline personality disorder: a systematic review of cross-diagnostic studies. Front Psychiatry. 2021;12:681876. PubMedCrossRef
Wessa M, Linke J. Emotional processing in bipolar disorder: behavioural and neuroimaging findings. Int Rev Psychiatry. 2009;21(4):357–367. PubMedCrossRef
Kupferschmidt DA, Zakzanis KK. Toward a functional neuroanatomical signature of bipolar disorder: quantitative evidence from the neuroimaging literature. Psychiatry Res. 2011;193(2):71–79. PubMedCrossRef
Malhi GS, Lagopoulos J, Sachdev PS, et al. Is a lack of disgust something to fear? a functional magnetic resonance imaging facial emotion recognition study in euthymic bipolar disorder patients. Bipolar Disord. 2007;9(4):345–357. PubMedCrossRef
Kluetsch RC, Schmahl C, Niedtfeld I, et al. Alterations in default mode network connectivity during pain processing in borderline personality disorder. Arch Gen Psychiatry. 2012;69(10):993–1002. PubMedCrossRef
King JB, Anderson JS, Yurgelun-Todd DA, et al. Decreased anterior cingulate activation in a motor task in youths with bipolar disorder. J Child Psychol Psychiatry. 2018;59(8):900–907. PubMedCrossRef
Chen CH, Suckling J, Lennox BR, et al. A quantitative meta-analysis of fMRI studies in bipolar disorder. Bipolar Disord. 2011;13(1):1–15. PubMedCrossRef
Hafeman DM, Bebko G, Bertocci MA, et al. Abnormal deactivation of the inferior frontal gyrus during implicit emotion processing in youth with bipolar disorder: attenuated by medication. J Psychiatr Res. 2014;58:129–136. PubMedCrossRef
Silvers JA, Hubbard AD, Biggs E, et al. Affective lability and difficulties with regulation are differentially associated with amygdala and prefrontal response in women with borderline personality disorder. Psychiatry Res Neuroimaging. 2016;254:74–82. PubMedCrossRef
Phillips ML, Ladouceur CD, Drevets WC. A neural model of voluntary and automatic emotion regulation: implications for understanding the pathophysiology and neurodevelopment of bipolar disorder. Mol Psychiatry. 2008;13(9):829, 833–857. PubMed
Yatham LN, Torres IJ, Malhi GS, et al. The International Society for Bipolar Disorders-Battery for Assessment of Neurocognition (ISBD-BANC). Bipolar Disord. 2010;12(4):351–363. PubMedCrossRef
Ridderinkhof KR, Ullsperger M, Crone EA, et al. The role of the medial frontal cortex in cognitive control. Science. 2004;306(5695):443–447. PubMedCrossRef
Welander-Vatn A, Jensen J, Otnaess MK, et al. The neural correlates of cognitive control in bipolar I disorder: an fMRI study of medial frontal cortex activation during a Go/No-go task. Neurosci Lett. 2013;549:51–56. PubMedCrossRef
Sripada CS, Silk KR. The role of functional neuroimaging in exploring the overlap between borderline personality disorder and bipolar disorder. Curr Psychiatry Rep. 2007;9(1):40–45. PubMedCrossRef
Laidi C, Houenou J. Brain functional effects of psychopharmacological treatments in bipolar disorder. Eur Neuropsychopharmacol. 2016;26(11):1695–1740. PubMedCrossRef
Zhang L, Li W, Wang L, et al. Altered functional connectivity of right inferior frontal gyrus subregions in bipolar disorder: a resting state fMRI study. J Affect Disord. 2020;272:58–65. PubMedCrossRef
McGrath CL, Kelley ME, Holtzheimer PE, et al. Toward a neuroimaging treatment selection biomarker for major depressive disorder. JAMA Psychiatry. 2013;70(8):821–829. PubMedCrossRef
Mel’nikov ME, Petrovskii ED, Bezmaternykh DD, et al. fMRI response of parietal brain areas to sad facial stimuli in mild depression. Bull Exp Biol Med. 2018;165(6):741–745. PubMedCrossRef
Quidé Y, Witteveen AB, El-Hage W, et al. Differences between effects of psychological versus pharmacological treatments on functional and morphological brain alterations in anxiety disorders and major depressive disorder: a systematic review. Neurosci Biobehav Rev. 2012;36(1):626–644. PubMedCrossRef
Petersen TJ. Enhancing the efficacy of antidepressants with psychotherapy. J Psychopharmacol. 2006;20(suppl):19–28. PubMedCrossRef