An MRI study of pituitary volume and parasuicidal behavior in teenagers with first-presentation borderline personality disorder

doi:10.1016/j.pscychresns.2007.12.003

Psychiatry Research: Neuroimaging

Volume 162, Issue 3, 15 April 2008, Pages 273-277

https://doi.org/10.1016/j.pscychresns.2007.12.003 Get rights and content

Abstract

This structural magnetic resonance imaging study examined the relationship between pituitary gland volume (PGV) and lifetime number of parasuicidal behaviors in a first-presentation, teenage borderline personality disorder (BPD) sample with minimal exposure to treatment. Hierarchical regression analysis revealed that age and number of parasuicidal behaviors were significant predictors of PGV. These findings indicate that parasuicidal behavior in BPD might be associated with greater activation of the hypothalamic–pituitary–adrenal (HPA) axis. Further studies are required using direct neuroendocrine measures and exploring other parameters of self-injurious behavior, such as recency of self-injurious behavior, intent to die and medical threat.

Introduction

Recurrent parasuicidal behavior (intentional, non-fatal self-injury, regardless of the intent to die (Linehan, 1997)) is a defining characteristic of borderline personality disorder (BPD) and up to 90% of BPD patients engage in threatened or actual parasuicide (Gunderson and Ridolfi, 2001). The BPD diagnosis is prospectively associated with parasuicidal behavior (Yen et al., 2004), with approximately 55–85% making at least one intentional, non-fatal self-injury with the intent to die (“suicide attempt” (Stanley et al., 2001)). In BPD, parasuicidal behavior is estimated to double the risk for suicide (Gunderson and Ridolfi, 2001), with around 8% completing suicide (Pompili et al., 2005).

The pathophysiology of suicide and parasuicide remains poorly understood. Hypothalamic–pituitary–adrenal (HPA) axis dysfunction has been implicated, with studies of completed suicide consistently showing HPA hyperactivity, whereas findings in attempted suicide are generally mixed (Lester, 1992) and might reflect the diagnostic heterogeneity of parasuicide. To our knowledge, no study has investigated the relationship between HPA axis functioning and parasuicide in BPD.

Pituitary gland volume (PGV) has been used as a measure of HPA axis activation (Sassi et al., 2001, Pariante et al., 2004, Garner et al., 2005). Animal studies have shown that increased levels of CRH lead to an increase in both the size and number of corticotrophs (ACTH-producing cells) in the pituitary (Westlund et al., 1985, Gertz et al., 1987). Hyperactivity of the HPA axis is frequently reported in patients with MDD and studies have revealed an increased PGV in this population (Krishnan et al., 1991, Macmaster et al., 2006b), which has been shown to correlate with circulating cortisol levels (Axelson et al., 1992).

Our investigation of PGV in a first-presentation, teenage BPD sample (Garner et al., 2007) found no difference in PGV between BPD and healthy control groups, although a history of childhood trauma might be associated with smaller PGV in BPD. The present study extends this research by investigating the relationship between PGV and number of lifetime parasuicidal behaviors in the same sample.

Section snippets

Participants

Twenty patients meeting DSM-IV criteria for BPD and aged between 15 and 19 years (mean age ± S.D. = 17.3 ±1.1 years; 5 male, 15 female) were recruited from a specialized early intervention program for BPD at ORYGEN Youth Health, Melbourne, Australia. The sample has been described in detail elsewhere (Chanen et al., in press). Participants had never received specific treatment for BPD and were physically healthy, based upon medical history. Potential participants were excluded from the study if they

Results

The mean (uncorrected) PGV was 506.9 mm³ (S.D. =113.0).

Bivariate associations between each predictor and PGV were examined. ICV and externalizing problems were only weakly associated with PGV (r < 0.156; NS). Weak associations were observed for the presence of mood disorders (present = 520.5 mm³ (S.D. 48.1); absent = 501.1 mm³ (S.D. 132.9); t = 0.344; df = 18; P = 0.735) and for the presence of anxiety disorders (present = 522.8 mm³ (S.D. 115.9); absent = 493.9 mm³ (S.D. 114.5); t = 0.558; df = 18; P = 0.584). Age (r =

Discussion

We found that a greater number of lifetime parasuicidal acts was significantly associated with a larger PGV in first-presentation BPD patients, possibly indicative of HPA hyperactivity. Previous literature has demonstrated a relationship between HPA hyperactivity and suicidality in patients with mood disorders (Coryell et al., 2006). The positive association between PGV and number of parasuicidal behaviors might reflect greater activation of the HPA-axis due to increased stress response by

Acknowledgments

The authors would like to thank the patients and staff of the HYPE Clinic at ORYGEN Youth Health, Ms Caroline Weinstein for assistance with data collection and Ms Susy Harrigan for statistical advice.

This work was supported in part by grants 98-0198 from the Victorian Health Promotion Foundation (VicHealth) and grant 990748 from the National Health and Medical Research Council (NHMRC). Neuroimaging analysis was facilitated by the Melbourne Neuropsychiatry Centre's Imaging Laboratory, managed by

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Childhood maltreatment, pituitary volume and adolescent hypothalamic-pituitary-adrenal axis – Evidence for a maltreatment-related attenuation
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Alterations of the development of the hypothalamic-pituitary-adrenal axis (HPAA) have been suggested to be related to experiences of early maltreatment. It has been postulated that early stress (i.e., maltreatment) leads to initial hyperactivation of the HPAA, which subsequently may progress to hypoactivation during the course of adolescence, however empirical studies on this hypothesis are rare. In the current study, we aimed to examine the longitudinal relationships between childhood maltreatment, early adolescent pituitary gland volume (PGV) and mid-adolescent cortisol output in an existing data set to explore the utility of PGV as a measure of HPAA function, and as an indirect test of the attenuation hypothesis.
The sample comprised 69 adolescents (30 females), subsampled from a larger longitudinal, community-based study on adolescent development. PGV, as an estimate of chronic childhood HPAA activity, was measured by magnetic resonance imaging during early adolescence (mean age 12.62 ± 0.45 years). Cortisol output was assessed via multiple salivary cortisol measures in mid-adolescence (mean age 15.52 ± 0.39 years). The cortisol awakening response (CAR) was calculated as a measure of HPAA functioning. Retrospective assessment of childhood maltreatment was performed using the Childhood Trauma Questionnaire (CTQ). Regression analyses were conducted to examine whether childhood maltreatment, PGV, and their interaction, predicted mid-adolescent CAR.
No main effect of PGV or maltreatment was found on adolescent CAR. PGV did however significantly interact with childhood maltreatment in predicting the CAR (t = −2.26; p = 0.024). Larger PGV positively predicted lower CAR in the context of relatively high childhood maltreatment (t = 2.032; p = 0.046), but showed no relationship in the context of relatively low maltreatment (t = 0.723; p = 0.472). Maltreatment also interacted with sex, such that (only) in females, higher levels of maltreatment predicted a lower CAR (t = −2.04, p = 0.042).
In the presence of childhood maltreatment, larger PGV was associated with lower CAR in adolescence, providing support for the application of PGV in studies of HPA axis function. Our finding is consistent with a maltreatment-related attenuation of HPAA functioning that may derive from a stress induced chronic hyperactivation during childhood. Prospective longitudinal studies are now required to further explicate these findings and relationships with psychopathology.
Structural and functional alterations of the suicidal brain: An updated review of neuroimaging studies
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Specific regions implicated in high lethality suicide patients were the right temporal gyrus, right orbitofrontal gyrus, right insular cortex, left fusiform gyrus, left lingual gyrus and right parahippocampal gyrus, in comparison to low lethality attempters. In another study by Jovev et al. (2008), however, pituitary gland volume was positively correlated with number of parasuicide events, implicating the hypothalamic-pituitary-adrenal (HPA) axis. A recent study by Kolla et al. (2016) showed that elevated monoamine oxidase A (MAOA) distribution volumes in individuals with BPD were significantly associated with the severity of mood symptoms and suicidal ideation.
Brain imaging is a non-invasive and in vivo direct estimation of detailed brain structure, regional brain functioning and estimation of molecular processes in the brain. The main objective of this review was to analyze functional and structural neuroimaging studies of individuals at risk for suicide. We reviewed articles published between 2005 and 2018, indexed in PubMed and Medline, assessing structural and functional alterations of the brain of individuals at high risk for suicide and at low risk for suicide. We reviewed functional and structural neuroimaging studies which included individuals with a history of suicidal ideation or attempt in major depressive disorder (MDD), bipolar disorder (BD), psychosis, and borderline personality disorder (BPD). We selected 45 papers that focused on suicidality in MDD, 17 papers on BD, 11 papers on psychosis, and 5 papers on BPD. The suicidal brain across psychiatric diagnoses seems to heavily involve dysfunction of the fronto-temporal network, primarily involving reductions of gray and white matter volumes in the pre-frontal cortex (PFC), anterior cingulate, and superior temporal gyrus. Nonetheless, there are several ways to define suicidal behaviour and ideation. Therefore, it still remains difficult to combine the evidence from imaging studies that used different definitions of suicidality.
Conceptualizing the neurobiology of non-suicidal self-injury from the perspective of the Research Domain Criteria Project
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Non-suicidal self-injury (NSSI) commonly starts in adolescence and is associated with an array of negative outcomes. Neurobiological research investigating NSSI is in its early stages and most studies have examined this behavior within the context of specific diagnoses. However, the Research Domain Criteria (RDoC) initiative encourages researchers to examine brain-behavior relationships across diagnoses. This review on the neurobiology associated with NSSI is organized using the domains proposed by RDoC: Negative Valence, Positive Valence, Cognitive, Social Processes, and Arousal/Regulatory Systems. Evidence of neurobiological anomalies is found in each of these domains. We also propose future research directions, especially in regard to human development. Future NSSI studies should address this behavior independent of diagnosis, examine relevant constructs across multiple units of analysis, and assess how systems change across development and course of illness. These advances will be essential for guiding neurobiologically informed intervention and prevention strategies to target NSSI. In doing so, we may prevent the associated negative outcomes across the lifespan.
Sex-specific prediction of hypothalamic-pituitary-adrenal axis activity by pituitary volume during adolescence: A longitudinal study from 12 to 17 years of age
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PGV is thought to increase with the number or size of corticotropin-releasing cells in the pituitary gland (Lorenzetti et al., 2009), which via ACTH release stimulate the release of cortisol by the adrenal cortex. Therefore, a larger PGV has previously been suggested to either predetermine, or reflect, the effects of chronically elevated HPAA activity (Jovev et al., 2008; MacMaster et al., 2006; Zipursky et al., 2011). Although salivary cortisol and PGV are each considered indicators of HPAA functioning, only two cross-sectional studies have been performed to date assessing the relationship between the two.
To investigate the longitudinal relationship between pituitary gland volume (PGV) and parameters of hypothalamic-pituitary-adrenal axis (HPAA) functioning during adolescence.
Participants were 49 adolescents (19 girls and 30 boys) selected from a larger longitudinal, population-based study of adolescent development. Assessments were conducted at three time points (S1, S2 and S3). MRI sessions were at S1 (age: M = 12.62, SD = 0.45 years) and S3 (M = 16.48, SD = 0.53 years) and multiple assessments of salivary cortisol were undertaken at S2 (M = 15.51, SD = 0.35 years). PGV was measured via previously validated manual tracing methods, and the cortisol awakening response (CAR) and diurnal slope (DSL) were used as indices of HPAA functioning.
A significant sex-linked interaction was found for PGV at S1 predicting both CAR (p = 0.025) and DSL (p = 0.009) at S2. Specifically, PGV at S1 significantly predicted CAR (p = 0.033) and DSL (p = 0.010) in boys only, with no significant results found for girls. Neither CAR nor DSL at S2 predicted growth of PGV from S1 to S3.
PGV in early adolescence predicted HPAA functioning in mid-adolescent boys but not in girls. The results suggest a significant influence of sex-specific development on the relationship between PGV and HPAA activity and reactivity. The findings have potential implications for understanding and interpreting sex-linked and stress related clinical disorders that emerge during mid-to-late adolescence.
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Brief reportAn MRI study of pituitary volume and parasuicidal behavior in teenagers with first-presentation borderline personality disorder

Abstract

Introduction

Section snippets

Participants

Results

Discussion

Acknowledgments

Psychiatry Research

Psychiatry Research

Biological Psychiatry

Psychiatry Research Neuroimaging

Journal of the American Academy of Child and Adolescent Psychiatry

Biological Psychiatry

Biological Psychiatry

Biological Psychiatry

Psychoneuroendocrinology

Manual for the Youth Self-report and 1991 Profiles

Manual for the Young Adult Self-report and Young Adult Behavior Checklist

Adaptive functioning and psychiatric symptoms in adolescents with borderline personality disorder

Journal of Clinical Psychiatry

Pituitary gland: MR imaging of physiologic hypertrophy in adolescence

Radiology

Brief report
An MRI study of pituitary volume and parasuicidal behavior in teenagers with first-presentation borderline personality disorder