The British Journal of Psychiatry (2019) 215, 395–403. doi: 10.1192/bjp.2019.44 Review Common and distinct patterns of grey matter alterations in borderline personality disorder and bipolar disorder: voxel-based meta-analysis Hua Yu*, Ya-jing Meng*, Xiao-jing Li, Chengcheng Zhang, Sugai Liang, Ming-li Li, Zhe Li, Wanjun Guo, Qiang Wang, Wei Deng, Xiaohong Ma, Jeremy Coid and Tao Li Background amygdala and right parahippocampal gyrus; patients with bipolar Whether borderline personality disorder (BPD) and bipolar dis- disorder showed decreased GMV and GMD in the bilateral medial order are the same or different disorders lacks consistency. orbital frontal cortex (mOFC), right insula and right thalamus, and increased GMV and GMD in the right putamen. Multi-modal Aims analysis indicated smaller volumes in both disorders in clusters To detect whether grey matter volume (GMV) and grey matter in the right medial orbital frontal cortex. Decreased bilateral density (GMD) alterations show any similarities or differences mPFC in BPD was partly mediated by patient age. Increased GMV between BPD and bipolar disorder. and GMD of the right putamen was positively correlated with Young Mania Rating Scale scores in bipolar disorder. Method Web-based publication databases were searched to conduct a Conclusions meta-analysis of all voxel-based studies that compared BPD or Our results show different patterns of GMV and GMD alteration bipolar disorder with healthy controls. We included 13 BPD and do not support the hypothesis that bipolar disorder and BPD studies (395 patients with BPD and 415 healthy controls) and 47 are on the same affective spectrum. bipolar disorder studies (2111 patients with bipolar disorder and 3261 healthy controls). Peak coordinates from clusters with sig- nificant group differences were extracted. Effect-size signed Declaration of interest differential mapping meta-analysis was performed to analyse None. peak coordinates of clusters and thresholds (P < 0.005, uncor- rected). Conjunction analyses identified regions in which disor- Keywords ders showed common patterns of volumetric alteration. Bipolar disorder; borderline personality disorder; grey matter; Correlation analyses were also performed. meta-analysis; distinct patterns. Results Patients with BPD showed decreased GMV and GMD in the Copyright and usage bilateral medial prefrontal cortex network (mPFC), bilateral © The Royal College of Psychiatrists 2019. Similarities and differences between bipolar and and the affective instability of BPD could originate from similar borderline personality disorder genetic aetiology as bipolar disorder. However, mood-stabilising The relationship between borderline personality disorder (BPD) medication is considered the key treatment intervention for and bipolar disorder remains controversial.1,2 Both are severe bipolar disorder, whereas psychotherapy is the key treatment for 22,23 mental disorders with a fluctuating course.3 Bipolar disorder is BPD. Furthermore, although the two conditions can co-occur, characterised by manic, depressive and mixed episodes, with inter- it is argued that their course, family history and treatment response vals showing varying levels of euthymic remission.4 BPD is defined are very different, and that misdiagnosis can result in patients not 24 as a long-standing pattern of functioning corresponding to a receiving appropriate treatment. disorder of personality.5 However, longitudinal study shows fluctu- ation with remission of symptoms, including affective instability.6,7 Neuroimaging studies of the two disorders Pervasive problems in affect regulation have been considered the – core feature of BPD by some researchers,8 11 with rapid switching In the absence of a definitive understanding of the neuropathology observed between different symptom profiles of anger, depression underpinning these two disorders, there are currently no clinical and anxiety.8,12 Symptom profiles and course of affective disturb- biomarkers available to aid diagnosis, clarify the relationship ance appear to differ.13,14 between bipolar disorder and BPD or indicate the most appropriate Clinical and community studies have shown high levels of diag- treatment. Biomarker discovery and optimization are therefore – nostic co-occurrence of the two disorders.15 17 A diagnosis of BPD essential. Neuroimaging studies have been used to identify differ- in young people can precede a diagnosis of bipolar disorder in adult- ences between patients with affective disorders and healthy controls 25,26 hood.18,19 It has also been suggested that BPD and bipolar disorder in structural magnetic resonance imaging (MRI) analysis. are alternative expressions of the same disorder,20 and that BPD is Changes in grey matter volume (GMV) and grey matter density on a bipolar spectrum of affective disorder,1,2,6,21 characterised by (GMD) in BPD have been most consistently found in the amygdala 27,28 ultra-rapid-cycling.5 It has been suggested that rapid switching and hippocampus; brain abnormalities in bipolar disorder are frequently reported within the frontal-striatal-limbic network.17,25 However, it is unclear whether changes in brain structure can differ- * These authors contributed equally to this work. entiate BPD from bipolar disorder, or whether common 395 Downloaded from https://www.cambridge.org/core. 23 Sep 2021 at 20:31:14, subject to the Cambridge Core terms of use. Yu et al abnormalities are present in both disorders.18 Only one study has independently, using keywords such as ‘borderline personality’, directly compared BPD and bipolar disorder, which found that ‘bipolar/affective/mood disorder’, ‘mania/hypomania/bipolar GMD changes in bipolar disorder were more diffuse and severe depression/’, ‘neuroimaging’, ‘mri’, ‘magnetic resonance’, ‘brain than in BPD, but had certain regions of overlap.29 To date, small imaging’, ‘morphometry’ and ‘voxel’. We followed Preferred sample sizes, heterogeneity and differences in analytical method Reporting Items For Systematic Reviews and Meta-analyses (e.g. whole-brain or region-of-interest (ROI) analyses) have resulted (http://www.prisma-statement.org)(Fig. 1) guidelines for meta- in inconsistency. A meta-analysis may provide a more precise evalu- analyses of observational studies.33 ation of potential diagnostic biomarkers at the brain level, clarify the Our inclusion criteria were as follows: (a) the study included uncertain relationship between bipolar disorder and BPD and patients with BPD versus healthy controls, and patients with ultimately improve classification.30 bipolar disorder versus healthy controls; (b) the VBM method The aim of this meta-analysis was to establish the most consist- was used to analyse whole-brain grey matter changes of patients ent brain function abnormalities of bipolar disorder and BPD, using with bipolar disorder and patients with BPD; (c) the study reported all published, whole-brain structural MRI studies that do not bias peak coordinates of the brain areas as well as the statistical paramet- findings to a priori hypothesised regions.31 ric maps, and coordinates were normalised into a stereotaxic stan- dardised space (e.g. the Montreal Neurological Institute (MNI) or Talairach space).34 Authors of published reports were contacted Method by email when required information was not provided. Our exclusion criteria were as follows: (a) neuroimaging Searches and study selection techniques other than MRI whole-brain VBM (using ROI/voxel- We conducted a literature search of PubMed (https://www.ncbi. of-interest methods might result in selection bias); (b) participants nlm.nih.gov/pubmed/), EMBASE (www.embase.com), Google aged <18 years or >65 years (to minimise effects of neurodevelopment Scholar (http://scholar.google.com/) and Science Direct (https:// and neurodegeneration); (c) patients diagnosed with schizoaffective www.sciencedirect.com/) for voxel-based morphometry (VBM) disorders or any comorbid neurological conditions; (d) review studies published between 1 January 2003 and 28 February 2018. papers or meta-analysis studies; and (e) when t-orz-maps were In addition, we conducted manual searches among the reference unavailable, consistent statistical thresholds throughout the brain sections of all retrieved studies and review articles.32 To ensure com- were not used or peak coordinates were not reported.25 For samples prehensiveness, two researchers performed the searches shared with other studies, the study with the largest sample was Bipolar disorder BPD structural studies structural studies (VBM) Identification (VBM) Articles identified Articles identified through database through database Articles excluded on the basis searching: Articles excluded on the basis searching: N of: of: N =37 - the technique of analysis =71 - the technique of analysis (diffusion tensor imaging) (diffusion tensor imaging) - the method of analysis (ROI -the method of analysis (ROI used) used) - the sample of individuals - the sample of individuals Screening examined Articles screened: Articles screened: examined N N - absence of coordinates =53 =23 - absence of coordinates N N =18 =14 Articles assessed for Articles assessed for Articles excluded to avoid Eligibility Articles excluded to avoid eligibility: eligibility: overlapping samples: overlapping samples: N =3 N =53 N =18 N =5 Studies included: Studies included: N =47 N =13 Included Articles included: N =60 Fig. 1 A Preferred Reporting Items For Systematic Reviews and Meta-analyses (PRISMA) flowchart of the article selection. PRISMA flowchart