Neuroligand binding endophenotypes in blood cells distinguish two subsets of borderline personality disorder patients

Begni, Barbara; Tremolizzo, Lucio; Andreoni, Simona; Contri, Margherita; Uccellini, Orlando; Neri, Francesca; Ferrarese, Carlo

doi:10.1016/j.neulet.2009.07.002

Cited by 10 publications

(12 citation statements)

References 22 publications

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“…This data might somehow arise from the fact that self-administered tools could be over- or underestimating the severity of a clinical trait or disease [22], and certainly BPD complex clinical presentations might be extremely challenging to be circumscribed [23]. The premise for a dysregulation of the neurosteroid system arose from our previous report of a decreased PK11195 binding in PBMC obtained from BPD patients [4]. Since the binding of this ligand assesses PBR (also known as TSPO) density, a defective synthesis of neurosteroids was hypothesized.…”

Section: Discussionmentioning

confidence: 99%

“…Following ethics committee approval of the study, both parents, besides all recruited subjects, gave written informed consent before undergoing the study procedures. The following scales were administered to each subject showing increased scores in BPD patients with respect to healthy controls (table 1): Children's Depression Inventory (CDI) [4,17] and State-Trait Anxiety Inventory form Y (STAI-Y) [18]. Moreover, the Borderline Personality Disorder Check List (BPDCL) was administered only to BPD patients [19].…”

Section: Methodsmentioning

confidence: 99%

“…Multivariate analysis was performed. Moreover, an attempt at calculating sample size for this pilot study was made a priori, based on our previously published plasma DBI data assessed in a healthy paediatric population [21], concurrently hypothesizing a plasma DBI change of 50% in BPD patients (similar magnitude with respect to the previously shown 65% reduction of PBR B max in PBMC [4], corresponding to the number of DBI cognate receptors). With α = 0.05, power (two-tailed) was high (>90%) hypothesizing of recruiting 12 subjects for group.…”

Section: Methodsmentioning

confidence: 99%

“…For these reasons, the concept of endophenotypes [3] has gained attention in the field of BPD, as in other complex disorders, in the attempt of dissecting this disease into more meaningful subgroups and of modelling specific traits that could be purposely targeted by dedicated drugs or novel therapeutic strategies. In a previous report [4], our group demonstrated that peripheral benzodiazepine receptor (PBR, also known as 18-kDa translocator protein or TSPO) expression on peripheral blood mononuclear cells (PBMC) might allow, at least in part, dissecting the neurochemical dysfunctions underlying different clinical presentations in BPD. In particular, PK11195 binding in PBMC was reduced in BPD patients with respect to controls, and a further reduction was present when dichotomizing BPD patients according to the presence of a depressive trait [4].…”

Section: Introductionmentioning

confidence: 99%

“…In a previous report [4], our group demonstrated that peripheral benzodiazepine receptor (PBR, also known as 18-kDa translocator protein or TSPO) expression on peripheral blood mononuclear cells (PBMC) might allow, at least in part, dissecting the neurochemical dysfunctions underlying different clinical presentations in BPD. In particular, PK11195 binding in PBMC was reduced in BPD patients with respect to controls, and a further reduction was present when dichotomizing BPD patients according to the presence of a depressive trait [4]. Interestingly, in this study, patients were medication free for at least a month, and most of them were even drug naïve, implying that the observed alterations reflected a process operative in the disease rather than drug-induced modifications.…”

Section: Introductionmentioning

confidence: 99%

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Diazepam Binding Inhibitor and Dehydroepiandrosterone Sulphate Plasma Levels in Borderline Personality Disorder Adolescents

Conti

Nacinovich²,

Bomba³

et al. 2013

Neuropsychobiology

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Background: Borderline personality disorder (BPD) patients display a complex and heterogeneous clinical phenotype that plausibly implies variable underlying pathogenic mechanisms. A dysregulation of peripheral benzodiazepine receptors has previously been shown in BPD peripheral tissues, implying possible alterations of its ligand, the diazepam binding inhibitor (DBI) or of the downstream products of its activation, i.e. neuroactive steroids. Methods: The aim of this work consisted in assessing, by ELISA, fasting plasma levels of DBI and dehydroepiandrosterone sulphate (DHEA-S), including cortisol and the cortisol-to-DHEA-S molar ratio (CDR), in 17 BPD adolescents versus 13 healthy controls, testing the possibility that clinical scales related to depressive or anxious traits (CDI, STAI-Y) or to disease severity (BPDCL) might be associated with a selective dysregulation of these parameters. Results: DBI plasma levels were unchanged, while DHEA-S ones were significantly increased (approx. 70%) and the CDR decreased in BPD patients. No meaningful correlations with clinical variables emerged. Conclusion: Our results indicate that a dysfunction of the neurosteroid system might be operative in BPD in spite of unchanged DBI plasma levels and that DHEA-S might represent a generalized trait marker for the altered stress response that is associated with this disorder.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Diazepam Binding Inhibitor and Dehydroepiandrosterone Sulphate Plasma Levels in Borderline Personality Disorder Adolescents

Conti

Nacinovich²,

Bomba³

et al. 2013

Neuropsychobiology

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Reduced fasting plasma levels of diazepam‐binding inhibitor in adolescents with anorexia nervosa

Conti

Tremolizzo

Bomba

et al. 2013

Intl J Eating Disorders

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Past, present, and future of genetic research in borderline personality disorder

Nia

Eveleth

Gabbay

et al. 2018

Current Opinion in Psychology

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Borderline Personality Disorder (BPD) is a major mental illness with a lifetime prevalence of approximately 1-3%, characterized by a persistent pattern of instability in relationships, mood, impulse regulation, and sense of self. This results in impulsive self-damaging behavior, high suicide rates, and severe functional impairment. BPD has a complex, multifactorial etiology, resulting from an interaction among genetic and environmental substrates, and has moderate to high heritability based on twin and family studies. However, our understanding of the genetic architecture of BPD is very limited. This is a critical obstacle since genetics can pave the way for identifying new treatment targets and developing preventive and disease-modifying pharmacological treatments which are currently lacking. We review genetic studies in BPD, with a focus on limitations and challenges and future directions. Genetic research in BPD is still in its very early stages compared to other major psychiatric disorders. Most early genetic studies in BPD were non-replicated association studies in small samples, focused on single candidate genes. More recently, there has been one genome-wide linkage study and a genome-wide association study (GWAS) of subclinical BPD traits and a first GWAS in a relatively modest sample of patients fulfilling full diagnostic criteria for the disorder. Although there are adequate animal models for some of the core dimensions of BPD, there is a lack of translational research including data from animal models in BPD. Research in more pioneering fields, such as imaging genetics, deep sequencing and epigenetics, holds promise for elucidating the pathophysiology of BPD and identifying new treatment targets.

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Neuroligand binding endophenotypes in blood cells distinguish two subsets of borderline personality disorder patients

Cited by 10 publications

References 22 publications

Diazepam Binding Inhibitor and Dehydroepiandrosterone Sulphate Plasma Levels in Borderline Personality Disorder Adolescents

Diazepam Binding Inhibitor and Dehydroepiandrosterone Sulphate Plasma Levels in Borderline Personality Disorder Adolescents

Reduced fasting plasma levels of diazepam‐binding inhibitor in adolescents with anorexia nervosa

Past, present, and future of genetic research in borderline personality disorder

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