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Research Article                                                                                                                                        Open Access

## If It Looks Like a Duck and Quacks Like a Duck: Evaluating the Validity of Borderline Personality Disorder in Adolescents

Carla Sharp 1* & Allison Kalpakci 2

1 University of Houston, The Menninger Clinic, Baylor College of Medicine, TX, USA 2 Developmental Psychopathology Lab, Dep. of Psychology, University of Houston, TX, USA

*Corresponding author: csharp2@uh.edu

## Abstract

Background: The validity of borderline personality disorder (BPD) has been a topic of much controversy in psychiatry. Over the last two decades, a wealth of empirical work has challenged long-held concerns regarding the validity of adolescent BPD. However, this research has been conducted within a traditional approach to psychiatric nosology.

Objective: In this article, we aim to evaluate the validity of adolescent BPD as guided by both the Robins and Guze criteria for the validity of psychiatric constructs and the new National Institute of Mental Health Research Domain Criteria (NIMH RDoC).

Method: We used the five principles of the Robins and Guze approach to evaluate selected research from our own and other  groups  regarding  the  validity  of  adolescent  BPD.  These  principles  include  clinical  description  studies,  laboratory studies, studies that delimitate the disorder from other related syndromes, follow-up studies, and family studies.

Results: Within the Robins and Guze criteria framework, evidence to date supports the validity of adolescent BPD to some extent. However, limitations of the research about the construct validity of adolescent BPD have also been identified, most notably  regarding  the  delimitation  of  adolescent  BPD  from  other  disorders  as  well  as  a  lack  of  longitudinal  and  family studies.

Conclusions: Given these limitations and the limitations  of  the Robins and Guze approach to psychiatric nosology, we recommend exploring the potential of the National Institute of Mental Health Research Domain Criteria as a complement to previous work.

Keywords: borderline personality disorder; adolescents; validity; developmental psychopathology

## Determining the Validity of a Psychiatric Disorder

In  2008,  Chanen  and  McCutcheon  published  a paper entitled, 'Personality disorder in adolescence: the diagnosis that dare not speak its name' (1). This title  speaks  to  the  concerns  that  were  present  as recently  as  six  years  ago  regarding  the  validity  of personality disorder (PD) in adolescents, specifically borderline  personality  disorder  (BPD).  Indeed,  at that time, the majority of British psychiatrists (63%) considered  the  diagnosis  of  adolescent  PD  to  be invalid  (2),  and  many  clinicians  still  appear  to  be uncomfortable diagnosing PD in adolescents (3).

Hesitations  regarding  diagnosing  this  disorder  in youth  are  based  on  sound  concerns.  Many  believe that a BPD diagnosis during adolescence engenders stigma  (4);  that  personality  is  inherently  unstable during adolescence (5,6); and that the clear demarcation  of  pathological  borderline  traits  from typical youth behavior (e.g., impulsivity, moodiness) is elusive (7). Specifically, adolescents undergo dramatic bodily changes, significant increases in the intensity of affective and emotional drives, and deep reorganization  of  the  self  in  the  context  of  peerdirected norms  and  interactions in addition to pressures toward autonomy and the assumption of adult roles (8,9). Further complicating the demarcation  of  BPD  from  normal  adolescence  is the fact that some of the behaviors that characterize adolescent  BPD  (e.g.,  self-harm,  substance  abuse, sexual risk-taking behavior) commonly occur during adolescence (10-12). These normative developmental changes resemble BPD to some extent and add  to  concerns  regarding  the  validity  of  a  BPD diagnosis in this age group.

But  how  do  we  determine  the  validity of a psychiatric disorder? In reaction to a lack of clarity surrounding  scientific  procedures  to  address  this question, in 1970, Robins and Guze (13) proposed a set of five principles that have since guided research regarding  the  nosology  of  psychiatric  disorder.  In contrast with heavy reliance on a priori hypothesized diagnostic criteria, which was a common part of early psychiatric disorder classification, the Robins and Guze method ensured that only through a series of systematically conducted  and  empirically  sound  studies  can  the suggestion  that  a  particular  diagnostic  entity  exists be substantiated. It is through this framework that much  of  the  work  over  the  past  few  decades examining BPD in both adults and adolescents has been  concentrated.  Although  they  were  published more  than  40  years  ago,  the  Robins  and  Guze criteria are still considered the gold standard approach for establishing the diagnostic validity  of psychiatric disorders.

The Robins and Guze  principles reflect the inclusion  of  five  types  of  research  studies,  each  of which is aimed at capturing a specific and separate component of a disorder's nosology:

- 1) Clinical  description  studies,  which  aim  to  establish  a coherent  clinical  picture  of  the  disorder. Studies  in  this category  must  demonstrate that  the  disorder  has  a particular  and  consistent  pattern  of  symptoms  and that these symptoms co-occur. Moreover, important non-psychopathological  features  that  are  common or prototypical of clinical presentations of the disorder must also be identified. These may include factors  such  as  age,  sex,  and  age  of  onset,  among others.
- 2) Laboratory studies, which focus on identifying neurobiological  and  physiological  substrates  of  the  disorder. Laboratory tests provide an important complement to  clinical  descriptive  studies,  especially  when  they confirm clinical observations.
- 3) Studies  that  delimitate  the  disorder  from  other  related syndromes. These studies pinpoint a disorder's uniqueness  relative  to  other  psychiatric  disorders with similar phenotypic presentations by establishing rates of co-occurrence with related disorders and supporting the discriminant validity of the construct.
- 4) Follow-up studies that identify a prototypical course and outcome  of  the  symptoms. For  example,  demonstrating that  individuals  who  were  first  identified  with  the disorder  in  baseline  assessments  present  with  the
5. same disorder (as opposed to a different psychiatric disorder) as identified by later assessments provides evidence for the original diagnostic criteria used at baseline.
- 5) Family  studies  that  identify  a  genetic  basis  of  the biological phenomena associated with the disorder. Demonstrating that the disorder displays heritability provides  evidence  for  distinct  psychopathological processes related to its phenomenology.

Over  the  past  two  decades,  much  of  the  work examining the validity of BPD  in  adolescents, including our own work, has been guided by these principles.  Although  these  guidelines  have  been crucial for advancing psychiatric research in general, the system is limited in its focus on the behavioral phenotype. In other words, it relies solely on observable  behavior  when  describing  psychiatric disorder  rather  than  understanding  the  disorder  in terms of its underlying processes and mechanisms. Analogizing from the animal world, after observing the physical  features  of  a  hippopotamus,  most would agree that the animal resembles the pig family and  thus  believe  that  the  pig  is  the  closest  living relative  of  the  hippopotamus.  However,  zoologists tell us that the closest living relative of the hippopotamus is the whale. Therefore, relying solely on  the  physical  features  of  a  phenomenon  when evaluating its validity can cause obvious problems.

In the case of psychiatric diagnosis, we deal with two specific problems that are characteristic of the Diagnostic  and  Statistical  Manual  of  Mental  Disorders (DSM)-based  categorical  and  polythetic  behavioral phenotype.  First,  psychiatric  diagnosis  is  based  on clinical observation and patients' phenomenological symptom self-reports. Unlike other medical disorders,  for  which  objective  diagnostic  tests  are used,  we  depend  on  patients'  perceptions  of  their problems  and  our  own  (sometimes  biased)  clinical observations. This is particularly problematic in the case of PD, because self-reported attributes cannot capture the dynamic processes that give rise to the discrepancies  between  self-identified  traits  and  the behavioral manifestations that are typically characteristic of PDs (14). Second, this implies that psychiatric  conditions  are  described  in  terms  of polythetic and dichotomous (categorical) diagnoses. This  means  that  patients  can  present  with  only  a portion of the criteria that define a disorder and will receive a certain diagnosis as long as they have met the predetermined symptom threshold (15).

The reliance on polythetic and dichotomous (categorical) diagnoses at the level of the behavioral phenotype  alone  has  led  to  concerns  about  the validity  of  the  nosological  system  -  most  notably the  problem  that  the  use  of  the  system  results  in high  rates  of  comorbidity  among  disorders,  over- reliance  on  disorder  'not-otherwise-specified'  or deferred  diagnosis,  and  lack  of  diagnostic  stability (15). Although there is much evidence in support of the DSM-based diagnostic system, some have expressed concerns that this system does not 'carve nature closely at its joints' (16) and thus may have impeded the use of advances in genomics, pathophysiology,  and  behavioral  science  to  aid  in the diagnosis and treatment of psychiatric disorders (17).  To  address  these  limitations,  the  National Institute  of  Mental  Health  (NIMH)  proposed  the Research  Domain  Criteria  (RDoC;18)  in  2011  to implement Strategy 1.4 of the National Institute of Mental Health Strategic Plan (19). By following this initiative, psychiatry would depart from its categorical classification system of mental disorders to 'develop new ways of classifying mental disorders  based  on dimensions of  observable  and neurobiological  measures'  (18).  In  this  article,  we evaluate the validity of BPD in adolescents according to both the traditional Robins and Guze criteria  and  the  newly  formulated  RDoC.  We  will focus on work emanating from our own laboratory as  well  as  from  other  laboratories.  We  begin  by discussing research organized within the framework of  the  five  Robins  and  Guze  criteria,  and  we  then evaluate the state of the science involving adolescent  BPD  against  these  criteria.  We  then discuss the RDoC principles and map directions for future research.

## Clinical Description

Categorical Diagnosis

Robins and Guze's first principle states that,  for  a disorder to be valid, its criterion set must constitute a coherent combination of traits and symptoms that 'hang  together'  (13).  Statistically  operationalized, this principle  requires  that a  single  common factor adequately accounts for covariation among  the criteria.  Studies  of  adults  (20-24)  and  adolescents (25) have factor analyzed the nine DSM borderline personality criteria and found evidence for a unidimensional  factor  structure  of  BPD.  With  this in  mind,  we  used  an  item  response  theory  (IRT) approach  to  examine  DSM-IV  BPD  criteria  in  a large community sample of young adolescents from the United Kingdom (N = 6339; M age = 11.75 years; 51.55% girls; 26). The use of IRT in this regard had several important advantages. First, because IRT is a latent  trait  approach,  it  allows  for  the  examination of  the  underlying  factor  structure  of  the  BPD criteria.  Second,  it  addresses  important  questions surrounding  DSM-IV  BPD  criterion  functioning. This process included examining  the extent to which a particular BPD  criterion discriminated among  adolescents  with  regard  to  their  standing along the continuum of BPD liability and whether certain criteria discriminate better than others. Third, it specifies the threshold of endorsement of a criterion along the latent continuum of BPD liability to determine  whether  certain criteria are  more difficult to endorse than others. Lastly, IRT allows for the examination of differences in the performance  of BPD  criteria across gender to determine  whether  the  BPD  criteria  are  useful  for both boys and girls.

In our study, BPD was assessed via the Childhood Interview for DSM-IV Borderline Personality Disorder (CI-BPD; 27). Results demonstrated that a single  underlying  dimension  adequately  accounted for covariation among the BPD criteria, which lends support to the unidimensionality of the  BPD construct. These findings were consistent with studies  from  the  adult  literature  (20-24)  and  with those of one study that used an adolescent sample (25). In addition, items demonstrated good discrimination  and  difficulty  parameters.  The  most difficult  items  included  abandonment  fears  and suicidal behavior; this finding converges with research in adults that has demonstrated that abandonment fears are the least commonly exhibited  BPD  symptom  (22,28)  and  that  suicidal behaviors  are  uncommon  among  young  children (29). With regard to measurement equivalence across  gender,  although  five  criteria  demonstrated differential  item  functioning,  this  balanced  out  at the level of the total set of the nine DSM-IV BPD criteria, which suggests that the use of the full nine criteria is psychometrically valid and advisable. Taken  together,  findings  from  this  study  provide evidence that the DSM criteria constitute a coherent combination of traits and symptoms, even in preadolescent and young adolescent youth, for whom the empirical base is less developed.

It is important to establish that a particular construct is valid across multiple samples so that it can  be  generalized  to  the  population  at  large.  The aforementioned  study  (26)  demonstrated  that  the CI-BPD  criteria  were  most  discriminating  at  the highest  level  of  underlying  borderline  personality pathology  liability;  this  finding  was  not  surprising given the community-based sample used. It cannot be  assumed,  however,  that  these  criteria  function similarly  in  a  clinical  setting  and  represent  a  valid approximation of the borderline personality pathology construct in clinical populations. Rather, there is a possibility that the aforementioned community sample findings capture psychopathology  or  distress  in  general  rather  than  BPD psychopathology  in  particular.  Thus,  we  revisited this question again with a sample of 190 inpatients ( Mage =  15.39;  9%  female;  33%  meeting  criteria  for BPD;  30).  We  used  a  confirmatory  factor  analytic approach to examine the internal factor structure of the  nine  CI-BPD  items.  The  internal  consistency (Cronbach's  alpha  =  .80),  the  inter-rater  reliability (kappa =  .89), the convergent  validity (with a clinician  diagnosis  kappa  of  .34  and  a pvalue  of <.001,  which  indicates  'fair  agreement'),  and  the concurrent  validity  were  examined  and  empirically supported as indicated by associations in the expected  directions  with  self-report  measures  of BPD traits, internalizing and externalizing pathology,  and  rates  of  self-harm  and  emotional dysregulation. Although we did not directly compare different models of underlying factor structures  with  one  another,  confirmatory  factor analytic  results  supported  a  unidimensional  factor structure  for  CI-BPD,  which  indicated  that  the DSM-IV  criteria  on  which  the  CI-BPD  is  based constitute  a  coherent  combination  of  traits  and symptoms, even among adolescents. This study was the largest inpatient study to examine the psychometric  properties  of  this  measure  among inpatient adolescents.

Factor analysis of the nine criteria in the absence of  other  PD  criteria  only  narrowly  establishes  the unidimensionality of the construct, which highlights an important limitation of the previously mentioned research. A more stringent test of unidimensionality would  involve the factor analysis  of  the  BPD criteria alongside Axis I or PD criteria. However, no work  of this nature has been conducted  with adolescents,  and  the  results  of  adult  studies  are mixed. In a minority of studies, the DSM structure of  PD  (ten  discrete  disorders,  including  BPD)  has been supported (31-34). Most studies have failed to support  the  DSM's  putative  structure  for  PD  (3538),  which  suggests  that  the  unidimensional  factor structure of BPD  may  disintegrate  after factor analysis  involving  other  PDs.  Recently  there  has been a growing interest in considering models that evaluate  general  factors  that  account  for  common variance  among  PDs  as  well  as  unique  sources  of variance that may represent more specific forms of personality pathology. From a factor-analytic perspective, this hypothesis can be tested with what is termed a bifactor model. This type of model allows PD  criteria  to  load  on  a  large  general  factor  that encapsulates  the  dysfunction  shared  across  PDs, with  additional  circumscribed  factors  that  capture the unique domains of impairment (39,40). To truly clarify  whether  DSM  criteria  hang  together,  factor analysis studies of this kind must be undertaken in adult and adolescent samples.

## Dimensional Self-Report Ratings

Although support for BPD as measured by clinical interview  (e.g.,  with  the  CI-BPD)  is  important, examining dimensional BPD traits is equally important, especially in the  context  of  DSM-5

Section III. Taking  a dimensional approach  to personality pathology assumes an individual difference  perspective  in  which  PD  pathology  is evaluated  through  quantitative  models  developed from  observable  traits  and  symptoms.  This  allows for  a  data-driven  approach  that  involves  the  data delineating the constructs. It also allows for a finegrained  description  of  personality  pathology  rather than lumping symptoms in predetermined categorical  diagnoses.  Finally,  as  demonstrated  in Section  III  of  the  DSM-5,  it  allows  for  a  hybrid model  of  personality  pathology  whereby  general personality  pathology  is  captured  by  Criterion  A (dysfunction  in  self-  and  other-relatedness)  and  in which specific disorders  and  traits  are  captured  by Criterion  B.  These  advantages  are  amplified  in  the context of BPD in adolescents. Specifically, dimensional measures are crucial for assessing BPD in youth precisely because of the concerns expressed earlier about categorical diagnosis during youth.  As  compared  with  categorical  approaches, dimensional  models  may  better  account  for  the developmental variability and heterogeneity common among adolescents and identify subclinical levels  of  BPD  for  early  intervention  (41).  These models also allow for the elucidation of heterotypic or  homotypic  continuity  of  the  disorder  (i.e.,  the relationship between BPD at one point in time with continued dysfunction at a later point), either through  BPD  pathology  or  a  different  form  of pathology. Finally, in contrast with semi-structured interviews,  which  often  are  expensive  and  timeconsuming  to  administer,  self-report  measures  are relatively  quick  and  inexpensive  to  administer,  and they  allow  the  evaluator  to  assess  a  wide  range  of behaviors  and  symptomatology  in  a  short  amount of time.

With the use of the Borderline Personality Features Scale for Children (BPFSC; 6) and an IRT approach, we examined the factor structure of traitbased BPD in a community sample of 881 adolescents  between  the  ages  of  13  and  17  years (55.9% female; 42). Given the putative factor structure of the BPFSC (6), we evaluated a bifactor model in which all items were allowed to load onto one  general  factor  and  in  which  respective  items were  allowed  to  load  onto  four  specific  factors: negative relationships, affective instability, selfharm, and identity problems. Results did not support a bifactor model; the 24 BPFSC items did not  load  onto  a  general  borderline  factor  or  onto predicted  subfactors.  Importantly,  strong  evidence for  local  dependence  between  items  (the  fact  that two or more items are more highly correlated with one  another  than  with  the  underlying  latent  trait) was exhibited, which suggests item redundancy. We therefore  removed  13  items  to  create  a  shortened version  of  the  BPFSC  (BPFSC-11)  and  tested  the factor  structure  of  this  truncated  measure.  With poorly functioning items removed, a unidimensional factor structure emerged. Moreover, when we tested the construct validity of the BPFSC-11 in a sample of 371 inpatient adolescents, it showed equivalence when  compared  with  the  longer  version  of  the BPFSC, including criterion validity against the interview-based  assessment  of  BPD  (i.e.,  the  CIBPD).

Further support for the construct validity of traitbased  conceptualizations  of  BPD  symptomatology during adolescence was provided in a study of 171 boys  between  the  ages  of  eight  and  18  years  who were  recruited  from  the  community  (43).  In  this study,  the  cross-informant  concordance  between parentand self-reported borderline personality features  using  the  BPFSC  and  a  newly  developed parent version of the measure (BPFSP) was examined. Results demonstrated modest but significant  concordance  between  parent-  and  selfreport ratings, and this was consistent with findings from other psychiatric constructs in child psychiatry (44).  Borderline  features  were  robustly  associated with  total  psychopathology  problems  as  measured by the Youth Self-Report and Child Behavior Checklist  (45)  as  well  as  by  specific  DSM-oriented scales.  Specifically,  boys  with  high  scores  on  the BPFSC  had  up  to  six  times  the  relative  risk  for overall psychopathology and up to five times greater risk as indicated by relative risk for specific psychopathology,  including  anxiety  disorder  (4.99), conduct disorder (4.59), attention-deficit/ hyperactivity disorder (3.88), affective disorder (2.86),  somatic  disorder  (2.65),  and  oppositional defiant disorder (2.22). Similarly, boys whose parent-reports  placed  them  in  a  high-BPD  trait group had up to nine times greater risk for externalizing disorders: conduct disorder (8.97), oppositional defiant disorder (3.67),  and  mood dysregulation (affective disorder [2.75]).

In another study involving the BPFSC, we examined  the  performance  of  parent-  and  selfreport  BPFS  tools  for  detecting  the  diagnosis  of BPD in 51 adolescent inpatients  between  the  ages of  12  and  18  years  (46).  This  study  made  use  of receiver operating characteristic analyses, which provide  receiver  operating  characteristic  curves  or the plot of the true-positive rate (sensitivity) against the false-positive rate (1-specificity) on a graph. The area under the curve (AUC) provides an indicator of accuracy.  Receiver  operating  characteristic  analysis was an advantageous approach in this study, because it allowed for the direct comparison of the relative performances of the BPSFC and BPFSP for predicting a CI-BPD diagnosis. Results demonstrated that  the  BPFSC  had  high  diagnostic accuracy (AUC = .93) for discriminating adolescents with  a  CI-BPD  diagnosis,  and  the  parent-reported version had moderate accuracy (AUC = .80; sensitivity = .73; specificity = .72). When comparing the  measures directly,  scores  from  the  BPFSC discriminated  significantly  better  than  did  scores from the BPFSP. Concordance between parent and child  reports  was  also  significant.  This  study  was important  in  that  it  provided  preliminary  support for the relative advantage of self-report over parentreport for the assessment of borderline traits during adolescence.  Given  that  BPD  is  suggested  to  be  a confluence of internalizing and externalizing psychopathology (47,48) and given that research has shown self-report to be more valid for internalizing disorders  during  adolescence  (whereas  parent-  or teacher-report may be more useful for externalizing problems [49]), we suggest that the superior performance demonstrated by the self-report BPFSC  in  our  studies may  be driven by the internalizing features of BPD.

## Screening Measures

If  BPD  assessment  is  to  be  routinely  included  in general adolescent assessment services, valid assessment tools for this purpose must be available. Although  the  BPFSC-11  would  perform  well,  the McLean Screening Instrument for Borderline Personality  Disorder  (MSI-BPD;  50),  which  was originally developed for adults, is another alternative.  The  MSI-BPD  is  a  10-item  self-report yes/no  measure  that  provides  a  brief  screening assessment  of  the  number  of  BPD  criteria  met.  It was designed specifically with low-resource settings in mind, where a quick and economical assessment of  BPD  is  necessary  for  potential  inclusion  in  a research study or for follow-up clinical assessment. We  examined  the  MSI-BPD's  ability  to  accurately identify  adolescents  with  BPD  using  the  CI-BPD and  the  BPFSC  in  a  sample  of  118  inpatients recruited  from  a  facility  that  serves  an  indigent population ( Mage = 14.64; 64.4% female) (51). At the bivariate  level,  results  demonstrated  that  the  MSIBPD was significantly related to both the CI-BPD and  the  BPFSC,  although  the  correlations  were  of moderate magnitude. Similar to results from a study conducted in a child and adolescent sample (52) as well as in a community sample of adult women (53), the  MSI-BPD  demonstrated  moderate  diagnostic efficiency  when  predicting  the  CI-BPD  diagnosis, with sensitivity (Sn) and specificity (Sp) values of .71 and .65, respectively, and diagnostic accuracy of .73. This study also established an MSI-BPD adolescentspecific cutoff score of 5.5, whereas the previously established  cutoff  score  of  7  rendered  in  the  adult sample  (53)  lowered  sensitivity  substantially  in  our sample (Sn = 48 and Sp = .83).

Summary

The  psychometric  work  involving  at  least  three measures  of  BPD  discussed  here  provides  some evidence  in  support  of  the  borderline  construct  in youth. Collectively, this work suggests that a coherent  clinical  picture  of  the  disorder can be described and that a particular and consistent pattern of symptoms co-occur even when they are assessed  using  different  measures.  Moreover,  our work and the work of others suggest that important non-psychopathological features (like those captured  by  prevalence  studies)  are  common  or prototypical  of  the  clinical  presentations  of  the disorder in adolescents. For example, the percentage of adolescent inpatients meeting the diagnostic criteria of the CI-BPD in our work mirrors that of other  studies  in  adolescent  inpatient  settings  that report  BPD  diagnostic  prevalence  rates  of  33%  to 53% (54-56).

However,  it  is  also  clear  that  further  work  is needed regarding the underlying factor structure of PD  in adolescents in general and in  BPD  in particular.  There  is  a  critical  need  for  evaluating more complex bifactor models in adolescent PD for both  categorical  symptom  and  dimensional  trait approaches to establish whether a coherent syndrome is present in adolescents. In other words, to firmly support the unidimensionality of a construct,  all  psychopathology  (including  all  PDs) must be considered. In the case of adolescent PD, this  agenda  is  complicated  by  the  fact  that  few DSM-based  measures  of  other  PDs  have  been developed  for  adolescents.  Although  the  CI-BPD and BPFSC  were developed for children and adolescents specifically, there are no developmentally  sensitive  counterparts  available  to assess  all  DSM-II-based  PDs.  This  is  necessary  to move DSM-based diagnostic work forward.

For  trait-based  approaches  to  PD  assessment  in adolescents,  the  picture  is  less  bleak.  There  are several adolescent trait-based instruments, including the  Minnesota Multiphasic Personality Inventory  Adolescent version (57), which is a 478-item true/false  self-report  inventory  designed  to  assess the social, emotional, and behavioral functioning of adolescents  between  the  ages  of  14  and  18  years that has been examined in one study of adolescent BPD  (58);  the  Dimensional  Personality  Symptom Item Pool (59), which is a 172-item measure structured to assess 27 maladaptive personality facets  that  are  hierarchically  organized  into  four broad personality dimensions (disagreeableness, emotional instability, introversion, and compulsivity);  and  the  adolescent  version  of  the Personality  Inventory  for  DSM-5  (60),  which  has recently  been  validated  for  use  in  adolescents  (61) and  which  includes  220  items  that  are  rated  on  a four-point Likert scale and structured into 25 empirically derived lower-level trait pathology facets that assess the traits associated with DSM-5 Section III.

## Laboratory Studies

Robins and Guze's second principle calls for laboratory studies that aim to identify neurobiological  and  physiological  substrates  of  the disorder. Although most laboratory studies of biological substrates of BPD have been conducted with  adults,  there  has  been  a  steady  increase  in biologically based studies involving adolescents. For example, laboratory studies of adolescent BPD have examined hypothalamic-pituitary-adrenal axis abnormalities. Kaess and colleagues (62), and Garner and colleagues (63) demonstrated that patients with BPD who were exposed to childhood trauma had smaller pituitaries (-18%) as compared with  those  with  no  history  of  childhood  trauma. Consistent  with  clinical  consensus  on  BPD,  these studies  suggest  that  the  hypersecretion  of  cortisol may be associated with maladaptive stress responses in the  development  of BPD,  especially in the presence of trauma history.

Structural functional neuroimaging studies in adolescents have demonstrated volume reduction in the frontolimbic network, including the orbitofrontal cortex (OFC), and the anterior cingulate  cortex  (ACC).  For  example,  Whittle  and colleagues (64) reported decreased left ACC volume in  15  female  adolescents  with  BPD  with  a  wide range  of  Axis  I  comorbidities,  and  Goodman  and colleagues  (65)  found  that  adolescents  with  BPD and  comorbid  major  depressive  disorder  (MDD) had  reduced  Brodmann  Area  (BA)  24  gray  matter volume as compared with healthy controls, but no differences were found in the size of the prefrontal cortex.  In  contrast,  Brunner  and  colleagues  (66) compared 20 adolescent girls with DSM-IV diagnoses of BPD, 20 patients with  DSM-IV defined current psychiatric disorders, and 20 healthy control subjects. The findings suggested that adolescent clinical control subjects displayed significantly  decreased  gray  matter  volume  in  the right  dorsolateral  prefrontal  cortex  as  compared with healthy control subjects, but no significant gray matter differences were detected between the BPD group  and  the  clinical  control  group.  Similarly,  no group differences were found in the limbic system or in any white matter structures. This study suggests  that  early  morphological  changes  in  BPD are located in the PFC but that these changes may not  be  specific  to  BPD,  because  changes  were similar to those found in the clinical control group. Finally,  Chanen  and  colleagues  (67)  compared  20 first-presentation BPD  patients and 20 healthy control  participants  and  found  a  reversal  of  the normal  (right  >  left)  asymmetry  of  orbitofrontal gray  matter  volume  in  the  BPD  group,  which reflects right-sided orbitofrontal gray matter loss in the BPD group as compared with control participants.  No  significant  differences  were  found for amygdala or hippocampus volumes. The authors suggested  that  hippocampus  and  amygdala  volume reductions  observed  in  adult  BPD  samples  may develop during the course of the disorder through early adulthood, but they acknowledged that longitudinal studies are needed  to  evaluate  this further.

Although  studies  of  the  biological  substrates  of BPD  are  important,  most  etiological  theories  of BPD favor a stress diathesis approach, which argues for an interaction between biological and environmental vulnerabilities in the development of BPD.  This  approach  is  also consistent with a developmental psychopathology  framework (68). When  considering  the  biological  underpinnings  of BPD and using an  attachment-  and  mentalizationbased  theoretical  framework  for  BPD  (69,70),  we have begun to explore the mentalizing deficits that may  underlie  interpersonal  dysfunction  associated with BPD in adolescents. According to this theoretical approach,  failures  or  impairments  in mentalizing  may  account  for  the  core  features  of BPD.  The  term mentalizing refers  to  our  ability  to interpret  the  behavior  of  others  and  ourselves  in terms  of  mental  states-that  is,  to  treat  ourselves and  others  as  psychological  agents  with  thoughts, feelings, desires, and so on (71). For optimal mentalizing capacity to develop, the child's attachment relationships play an important role, and disruptions of early  attachment  experiences  can derail social-cognitive development, thereby leading to  BPD  (72).  In  this  model,  emergent  mentalizing capacity is the result of both biological and genetic factors (inherited theory of mind  capacity and sensitive  temperament)  and  environmental  factors (adverse  or  mismatched  family  environment).  A recent  meta-analysis  of  functional  brain  imaging studies of theory of mind (73) identified the existence of a 'core network'  for  mentalizing, including the medial prefrontal cortex (mPFC) and the  bilateral  posterior  temporal  parietal  junction (TPJ).  Although  work  in  our  laboratory  has  yet  to incorporate the biological  level  of  explanation  into study designs, we have begun examining mentalizing correlates of BPD in adolescents at the behavioral phenotypic level.

For instance, we used the Movie for Assessment of Social Cognition (MASC;74) in a sample of 132 inpatient  adolescents  ( Mage =15.5;  62%  girls;  23% meeting  criteria  for  BPD;75)  to  assess  mentalizing capacity.  During  the  administration  of  this  tool, research subjects watch a 15-minute movie of four characters  interacting  around  interpersonally  and emotionally  salient  topics.  The  movie  is  paused multiple  times,  and  research  subjects  are  asked  to reflect  on  the  thoughts  and  feelings  of  the  movie characters. Four mutually exclusive mentalizing styles are provided: no mentalizing (no reference is made  to  mental  states  to  understand  or  explain characters' behavior), undermentalizing (some reference is made to mental states, but it falls short of  fully  capturing  the  nuance  of  the  interpersonal situation), hypermentalizing (mental states are overattributed,  and  inferences  are  based  on  little  or  no existing evidence), and accurate mentalizing. Results demonstrated  that,  of  all  four  mentalizing  styles, only hypermentalizing was associated with borderline  traits;  this  behavior  also  distinguished subjects who met criteria for BPD from those who did not.

In a follow-up study, we measured hypermentalizing at discharge in a larger sample  of adolescents from the same inpatient unit. Here, we demonstrated a significant reduction in hypermentalizing, which was associated with a significant reduction  in  borderline  traits  (76).  Importantly,  in this study we assessed other forms of mentalizing at admission and discharge as well, given the fact that mentalizing is a multifaceted construct. These forms of mentalizing included explicit mentalizing through an emotion recognition task, empathy, and pseudomentalizing. Only pseudomentalizing showed similar associations with borderline symptom  reduction, although these associations were  not  as  significant  as  those  associated  with hypermentalizing.  That  both  hypermentalizing  and pseudomentalizing were sensitive to treatment effects was not surprising, because both hypermentalizing and pseudomentalizing are considered to be indices of what Fonagy and Luyten (77) consider to be the 'pretend mode' in mentalization  theory.  Pretend  mode  is  a  form  of impaired mentalizing in which thoughts and feelings become severed from reality. Pseudomentalizing in particular  involves  the  use  of  mental  states  that appear  to  be  rooted  in  reality  but  that,  on  closer examination, are found to be suspended from it.

## Summary

Although  the  above  studies  were  important  to establish the initial empirical evidence for mentalizing impairment associated with BPD in the specific form of hypermentalizing, they are far from establishing the biological basis of adolescent BPD from  the  perspective  of  mentalizing  capacity.  For this  to  occur,  the  biological  level  of  explanation must be integrated into mentalization-based studies of  adolescent  BPD  in  the  form  of,  for  instance, neuroimaging. Such studies have been conducted in adults  (e.g.,78),  and  they  demonstrate  the  potential of the mentalizing construct to serve as a laboratory-assessed biological correlate  of  BPD. Other potential targets for laboratory studies in the Robins and Guze framework include reward function (79) and emotion dysregulation (80). Of all the Robins  and  Guze  principles,  the need  for laboratory  studies  to  establish  the  neurobiological substrates  of  a  disorder  is  perhaps  most  strongly compatible with the RDoC, which we will return to later in this review.

## Delimitation from Other Disorders

A particular  challenge  for  the  validity  of  BPD  has been  its  high  comorbidity  with  other  disorders. Earlier,  we  discussed  how  the  BPD  criteria  have been factor analyzed with other PDs in an attempt to  demonstrate  that  BPD  is  a  discrete  disorder. These  studies  were  conducted  due  to  the  high comorbidity between BPD and other PDs, but they did not replicate the DSM-based 10-factor structure for  PD.  Adult  BPD  demonstrates  equally  high comorbidity with both internalizing and externalizing disorders (81-88), and adolescent studies  have  found  similar  patterns  of  comorbidity (89-91).  These  high  rates  of  comorbidity  suggest that underlying structures may account for observed comorbidity (covariance) among  disorders (47). James and Taylor (48) found that BPD served as a multidimensional indicator of both the externalizing dimension and the anxious-misery (distress) subfactor of the internalizing dimension across both genders. Using more rigorous assessment tools and a larger and more  diverse sample, Eaton  and colleagues (47) replicated this finding, again in both genders.  We  recently  attempted  to  replicate  these findings  in  a  sample  of  434  adolescent  inpatients. With  the  use  of  a  confirmatory  factor  analytic approach,  we  found  support  for  the  notion  that adolescent BPD is a confluence of internalizing and externalizing  pathology  (92).  Broadly speaking,  our findings replicated those of both Eaton and colleagues (47) and James and Taylor (48): adolescent BPD loaded onto both internalizing and externalizing dimensions, and this finding was robust  across  both  genders  while  retaining  unique variance  in  the  model.  In  other  words,  complete overlap with internalizing and externalizing disorders did not occur.

## Summary

That BPD appears to be a confluence of internalizing and externalizing disorders (47), despite  retaining  unique  variance,  challenges  the notion that BPD can be successfully delimited from other disorders. These findings point to the value of taking  a  dimensional  approach  to  psychopathology in  general  and  personality  pathology  in  particular, because this allows for the cross-loading of components of disorder onto common latent factors.  Therefore,  in  contrast  with  a  categorical approach  that  requires  the  demonstration  of  BPD as a discrete disorder, the dimensional approach can describe how features of BPD may be shared with other clinical syndromes and personality pathology. We have begun to explore such models in the field of  adolescent  BPD,  and  much  work  is  still  to  be done. However, it is becoming clear that the Robins and Guze requirement of discrete categorical diagnostic  entities  may  not  reflect  the  reality  of psychopathology.

## Follow-Up Studies

Robins  and  Guze's  fourth  principle  suggests  that studies  should  be  conducted  that  demonstrate  a prototypical course and outcome of the symptoms. Although  there  is  an  urgent  need  for  prospective studies of BPD,  research conducted by other groups provides evidence for a prototypical course and  outcome  of  adolescent  BPD  symptoms.  For example,  research  has  pinpointed  the  age  of  13 years  as  a  typical  age  of  onset  for  BPD  (93). Although it is true that adolescence is characterized by a high prevalence of all psychiatric disorders (94), adolescence appears to be a particularly vulnerable period for BPD,  hence  the urgent calls from research  for  early  intervention  (41).  As  with  all psychiatric disorders, an early onset of BPD usually denotes poorer outcomes (95). With its onset during adolescence, BPD then typically peaks during early adulthood and subsequently declines (96). Moreover,  research has  suggested a heterotypic developmental course for BPD; this involves coherence with regard to the underlying organization or meaning of behaviors over time (as opposed to homotypic continuity, where coherence is  evident  at  the  level  of  the  behavioral  phenotype [97]). Specifically, it appears that externalizing features  are  most  strongly  manifested  early  during the course of BPD (98), with internalizing features becoming  more  prominent  throughout  adulthood (47).  Similar  to  the  course  of  adult  BPD,  stability appears  to  be  moderate  with  adolescent  BPD  (99101).

## Summary

Although research is sparse, preliminary evidence is strong for Robins and Guze's fourth criteria for the validity of psychiatric disorder. Research has demonstrated the comparable stability  of  BPD among adolescents, which has also been demonstrated  for  adults  (99),  as  well  as  a  typical course, which involves symptoms appearing during adolescence,  peaking  during  early  adulthood,  and then declining (96).

## Family Studies

Robins and Guze's fifth principle states that family studies must identify a genetic basis for the biological phenomena associated with the disorder. Several  genetic  studies  have  been  conducted  for BPD in adults, and these studies have demonstrated moderate  heritability (96).  Distel  and  colleagues (102) estimated a heritability of .42 in an adult twin design,  and  heritability  rates  of  .69  (103)  and  .60 (104) were demonstrated in other studies. Recently, two studies have been conducted involving adolescents.  The  first  study  (105)  made  use  of  a longitudinal  birth  cohort  sample  of  1116  pairs  of same-sex twins who were assessed from the ages of 5 to 12 years. The study aimed to demonstrate the consistency of the cause of borderline personalityrelated characteristics  (BPRCs)  in  children with theoretical  models  of  the  causes  of  adult  BPD. Results  demonstrated  that,  at  the  age  of  12  years, mother-reported  BPRCs  were  correlated  at  0.66 among  monozygotic  twins and at 0.29  among dizygotic  twins,  with  findings  pointing  to  genetic factors  accounting  for  66%  of  the  variance  in BPRCs. In addition, children categorized as belonging  to  an  'extreme  borderline  group'  (i.e., having more BPRCs) at the age of 12 years were the same  children  who,  at  the  age  of  5  years,  had significantly lower levels of intelligence, self-control, and theory of mind and higher levels of impulsivity, externalizing, and internalizing problems. These children also had high rates of co-occurring conduct disorder, depression, anxiety, and psychosis. Finally, consistent with a diathesis-stress model, exposure to harsh  treatment  in  the  family  environment  (e.g., physical  maltreatment,  maternal  negative  expressed emotion)  through  the  age  of  10  years  predicted BPRCs  as  well  as  categorization  in  the  'extreme borderline'  group  at  the  age  of  12  years.  This finding suggested that environmental mediation was stronger  among  children  with  a  family  history  of psychiatric illness. Taken together, this study provides  important  evidence  for  a  genetic  basis  of borderline-related traits. Perhaps more importantly, it  provides  evidence  for  the  interaction  between genetic and environmental influences on the emergence  of  borderline-related  traits  in  youth,  a finding that is consistent with etiological models of

adult BPD.

In the second study (106), the longitudinal course and heritability of BPD traits were examined over a 10-year period beginning at the age of 14 years and ending  at  the  age  of  24  years  using  a  twin  design. Mean-level BPD  traits were found to decline significantly  from  adolescence  to  adulthood,  but rank order stability remained high. BPD traits were moderately heritable at  all  ages,  with  a  slight  trend toward  increased  heritability  from  the  age  of  14

years to the age of 24 years.

Although several candidate genes have been implicated for adult BPD (e.g., tryptophan hydroxylase [107], 5HT2a [108], 5HT2c [109], monoamine oxidase [110]), thus far, only one study has examined  genetic  polymorphisms  associated with  adolescent  BPD.  In  a  replication  of  findings from  adults  with  BPD,  an  association  between  5HTTLPR and BPD traits in children and adolescents between the ages of 9 and 15 years were demonstrated;  carriers  of  the  short  allele  of  5HTTLPR exhibited the highest levels of BPD traits (111).

## Summary

Since 1970, when Robins and Guze published their article calling for a systematic approach to establishing the validity of psychiatric disorder, research  in  the  fields  of  behavioral  and  molecular genetics and the neurosciences have been revolutionized.  At  that  time,  one-to-one  relations between genotypes and psychiatric phenotypes were thought possible, and gene-environment interactions in psychiatric disorders may have been considered  but  certainly  not  modeled.  Today,  we know that, for most psychiatric disorders (including BPD), evidence supports a view that constitutional factors (e.g., temperament) and environmental factors  (e.g.,  family  factors)  both  have  etiological roles.  For  example,  in  an  innovative  recent  study using a twin design (112), the temperamental traits of  behavioral  disinhibition  or  externalizing  (EXT; impulsivity and inability to inhibit undesirable actions)  and  negative  emotionality  or  internalizing (INT; predisposition to experience depression, anger,  and  anxiety)  in  interaction  with  child  abuse (CA)  to  predict  borderline  traits  over  time  was investigated.  Three  causal  models  were  tested:  a direct causal model (CA  BPD), a diathesis stress model  (INT/EXT  x  CA  BPD),  and  a  genetic mediation  model  where  the  CA-BPD  association was  better  accounted  for  by  common  genetic  risk factors (i.e.,  INT, EXT, or additive INT and EXT psychopathology could account for genetic or environmental influences common  to CA  and BPD). The authors found the strongest support for a genetic mediation model in which the association between  exposure  to  traumatic  events  and  BPD may  be  better  accounted  for  by  common  genetic influences rather than the former causally influencing the latter.

More studies of gene/biology-environment interactions are now needed. There is also an urgent need  for studies that consider  more  than  one biological  level  of  explanation  simultaneously.  The limitations  of  the  Robins  and  Guze  approach  are clear,  and  we  can  now  turn  our  attention  to  the NIMH's answer to these limitations.

## National  Institute  of  Mental  Health  Research Domain Criteria

In  the  above  review  of  the  Robins  and  Guze criteria, we  have shown  that the construct of adolescent  BPD  meets  some  of  these  criteria.  For example, there is some evidence for the unidimensional factor structure of adolescent BPD (although  we  acknowledge  that  this  evidence  was found  at a low  threshold), and  there is  some evidence for neurobiological correlates that are specific to adolescent BPD. We have also discussed research that demonstrates a meaningful course for the disorder during adolescence. However, the discussion of the Robins and Guze criteria has also revealed  limitations of the construct  validity of adolescent  BPD.  These  limitations  may  be  due  to the  fact  that  BPD  is  an  invalid  construct  during adolescence.  However,  limitations  may  also  be  the result  of  the  possibility  that  the  Robins  and  Guze criteria are not an appropriate yardstick for evaluating the validity of psychiatric disorders. It is in  this  context  that  we  now  turn  to  an  alternative approach to developing and evaluating the construct validity of psychiatric disorders.

The NIMH developed the RDoC in response to long-held criticisms of the DSM system of validating psychiatric disorder, which, as we discussed,  was  informed  by  the  Robins  and  Guze criteria.  In  contrast  with  this  system,  the  RDoC does not subscribe to a categorical system but rather propagates  a  dimensional  system  that  spans  the range from typical to atypical behavior. In addition, although the DSM system of diagnostic criteria was by  and  large  determined  by  consensus  (15),  the RDoC are agnostic with regard to DSM categories. Instead, the RDoC seeks to generate classifications from  basic  behavioral  neuroscience.  Whereas  the Robins and Guze system sought to find the neurobiological  substrates  for  DSM  diagnosis,  the RDoC's  starting  point  is  knowledge  of  behaviorbrain  relations  that  can  then  be  linked  to  clinical phenomena;  this  is  typically  based  on  dimensional ratings that cut across different psychiatric disorders (17). To this end, the RDoC provides a matrix with rows that cover five domains of function: negative valence systems, positive valence systems (approach/motivation),  cognitive  systems,  systems for social processes, and arousal/regulatory systems. Each  of  the  domains  is  associated  with  relevant constructs selected for the potential that a particular brain circuit or area could reasonably be specified to implement that dimension of behavior. For example

(and  of  most  relevance  to  the  laboratory  studies described previously), the RDoC systems for social processes include the following constructs: imitation, theory of mind (mentalizing), social dominance, facial expression, identification, attachment/separation fear, and self-representation. The columns of the matrix represent seven different units of analysis: genes,  molecules,  cells,  neural circuits, physiology, behaviors, and self-report. The idea is that researchers would study these constructs across psychiatric disorders and make use of latent trait  analyses  to  'carve  nature  more  closely  at  its joints.'This  is  done  in  the  hope  that  we  would develop over time a more valid nosology of psychiatric disorder.

To  our  knowledge,  the  RDoC  has  not  yet  been applied  to  either  adult  or  adolescent  BPD.  We believe,  however,  that  the  RDoC  system  holds promise for further evaluating and establishing the validity of BPD during adolescence.

## Future Research Directions

In  this  article,  we  have  presented  some  of  the research that we have conducted in our  own laboratory  as  well  as  the  research  conducted  by others to evaluate the validity of BPD in adolescents.  Like  most  research  in  psychiatry,  our work has been guided by the influential Robins and Guze criteria for the validity of psychiatric disorder. As  discussed,  the  limitations  of  this  approach  are now well acknowledged, and the question arises as to  how  we  can  advance  knowledge  regarding  the validity  of  adolescent  BPD  within  the  new  NIMH RDoC framework. A natural first step is to abandon studies that recruit subjects based on the inclusion criterion of a BPD diagnosis. Instead, large cohorts of patients and non-patients who represent a broad spectrum of psychiatric diagnoses should be recruited. Like recent studies that make use of latent trait approaches to locate BPD within the internalizing/externalizing spectrum (47,48,92) or to evaluate  BPD  in  the  context  of  other  PDs  (113), studies  of  adolescent  BPD  must  recruit  across  the full spectrum of typical/atypical behavior. Measures that  assess  the  behavioral  phenotype must then be used  alongside  biological  measures  and  preferably across  multiple  levels  (e.g.,  genes,  molecules,  cells, neural  circuits,  physiology).  Multivariate  statistics can then be employed to find patterns of covariation  among  variables.  Latent  class  analyses can  also  be  employed  if  a  more  person-centered approach  is  preferred.  This  enterprise  is  risky  not only for BPD  but also for other psychiatric disorders, because findings may challenge our longheld  implicit  belief  system,  which  guides  everyday clinical decision making.  Alternatively, to better understand  and  effectively  treat  psychiatric  illness, we  must  be  willing  to flexibly  expand  on  the foundational work that has been conducted during the past 40 years. Making the decision to embark on this endeavor may  in time leave us pleasantly surprised.

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