The main findings of this family interview study of BPD were that BPD and its 4 sectors of psychopathology aggregate in families and that the relationship among these sectors is best explained by a common pathway model in which the sectors represent manifestations of a latent BPD construct.
We discuss these findings in turn. Our primary hypothesis—that BPD (meeting both DSM-IV
and DIB-R criteria) is caused in part by familial factors—was strongly supported. An individual with a first-degree relative showing BPD exhibited a statistically significant 3- to 4-fold increase in risk of BPD compared with an individual without a first-degree relative with BPD. In addition, we found a substantial and statistically significant correlation of 0.28 to 0.37 for the presence of BPD between pairs of first-degree relatives. These results are consistent with previous, less methodologically rigorous, family studies13–22
that have also found evidence of familial aggregation of BPD and with twin studies23–26
that have found evidence of substantial heritability of BPD. Taken together, these results indicate that familial factors contribute importantly to the development of BPD.
We also found that each of the 4 sectors of BPD psychopathology aggregated in families. The correlation between family members was greater for the affective and interpersonal sectors (using the DIB-R but not the DSM-IV definition) than for the behavioral and cognitive sectors. These differences could reflect differences in the strength of familial factors for different sectors but also could be the result of differences in the ability of the measures to tap the underlying construct of interest or heterogeneity within the sectors. Notably, the level of familial aggregation, as assessed by the correlation between pairs of relatives, was less for each of the sectors than it was for BPD. As with the diagnosis of BPD, the level of familial aggregation for sectors was higher for DIB-R–derived definitions than it was for DSM-IV–derived definitions.
Although family study data, unlike twin study data, cannot be used to identify the proportion of familial factors caused by genetic factors and those caused by the common family environmental factors without strong additional assumptions,76
there are 2 reasons to suspect that genetic factors largely account for the familiality of BPD. First, most importantly, twin studies of BPD23–26
and of the sectors of BPD psychopathology,44,45,47,72
have found no evidence of a significant contribution of common family environment. Similarly, we found no consistent differences in the level of familial aggregation between types of relative pairs (eg, siblings vs parent-child), whereas such differences would be expected if common family environmental factors were present. However, this latter argument is tentative because of inherent limitations of the family study design to address this issue; furthermore, to the extent that family study data can be used for this purpose, we had limited power to detect effects of interest.
Based on the reasonable likelihood that common family environmental factors are negligible, our data can be used to derive estimates of heritability. By doubling the observed correlation coefficients (because first-degree relatives share, on average, 50% of their genes, the correlation due to sharing 100% of genes would be twice that observed among first-degree relatives), we obtain heritability estimates for BPD of 55% (using proband-relative pairs) and 74% (using all pairs of relatives) and estimates for sectors ranging from 26% to 60% using the DIB-R definitions and 14% to 44% using the DSM-IV
definition. Estimates from twin studies for the heritability of BPD range from 37% to 69%23–26
and estimates of the sectors’ affective instability, impulsiveness (similar to behavioral in this study), and cognitive range from 31% to 49%44–47
; all of these estimates lie within the 95% confidence intervals of our estimates.
We note further that the findings from our family study and those from registry-based twin studies23,24,26
are not only convergent but also complementary with respect to the methodologic strengths of the 2 designs, with our study providing evidence based on more rigorous assessments using direct interviews and more information derived from full cases of BPD, and the twin studies providing data that are less vulnerable to selection bias and evidence that the familial effects are due to genetic factors.
Although genetic factors likely play a role in BPD, no genetic mechanisms underlying BPD or specific genes associated with BPD have been identified. However, one linkage study77
has found an association of BPD with a region on chromosome 9 that contains a number of plausible candidate genes.
Addressing the relationship among the 4 sectors of BPD psychopathology, we found that the pattern of co-occurrence of sectors within individuals and aggregation of sectors between family members was better explained by a common pathway model than by an independent pathway model. For the models with DIB-R–defined sectors, the difference in AIC was very modest and thus indicated an essentially equivalent overall fit. The overall fit evaluated by BIC, which penalizes lack of parsimony more than the AIC, was much better with the common pathway model for both sets of models. On balance, our data suggest that the common pathway model is the best-fitting model.
Under the plausible assumption that the contribution of common family environment is negligible, the heritability of the latent factor of BPD-ness from the common pathway model was 43.9% using DSM-IV
–defined sectors and 58.6% using DIB-R–defined sectors. Two other studies that performed this type of analysis also found support for the common pathway model over the independent pathway model and yielded similar estimates (51%44
) for the heritability of the latent BPD construct. Distel and associates44
assessed 4 sectors of BPD derived from the Personality Assessment Inventory Borderline Features scale (affective instability, negative relationships, identity problems, and self-harm), and Kendler and colleagues54
assessed 4 sectors derived from the Dimensional Assessment of Personality Pathology–Basic Questionnaire (affective lability, insecure attachment, cognitive dysregulation, and identity problems). Taking the findings of these studies together with those of our study (which again are not only convergent but also stem from methodologically complementary designs) favors the hypothesis that the relationship between the sectors is better explained by their being manifestations of an underlying latent BPD construct rather than the alternative hypothesis that the sectors themselves are the primary psychopathological entities.
Our modeling results should be interpreted with caution. The number of sectors was small and, although major sectors of BPD were captured, other potentially important elements of BPD psychopathology were not assessed. Therefore, it was possible to fit only 1 independent pathway model with a single common familial factor and a single common environmental factor. With a larger sample and a more fine-grained analysis, using a larger number of sectors (and even exploration of traits within the sectors, since each sector embraces a broad range of traits), it is possible that an independent pathway model with more than 1 common familial or environmental factor would provide a better fit. Furthermore, the latent construct of BPD might prove to be better conceptualized as a liability to more general personality psychopathology. For example, Distel and associates78
found considerable overlap in the genetic and environmental factors for BPD and for 4 of the 5 dimensions of the 5-factor model.79,80
In addition, Livesley and colleagues46
identified, through factor analysis and multivariate twin analyses, a higher-order personality factor, termed emotional dysregulation
, that included not only affective instability, cognitive dysregulation, and other features in common with BPD but also a broader range of psychopathology.
These caveats notwithstanding, the evidence for a common pathway model with a unitary liability to BPD, combined with our finding that the familiality of BPD is greater than that of its individual sectors, has 3 implications. First, there should be efforts to identify endophenotypes associated not only with individual sectors of BPD37,72
but also with a more global tendency toward dysregulation that involves several sectors. Second, treatments should be developed to target multiple sectors of BPD, and, conversely, treatments directed at individual sectors of BPD may not be optimally targeting factors that underlie those sectors. Third, the proposed radical change to either a dimensional or a prototypic definition of BPD for DSM-581,82
should await evidence that the proposed revisions define a construct with better clinical usefulness, familiality/heritability, and psychometric coherence than the definition of BPD in DSM-IV
. Based on these indices, a better definition might be one that requires psychopathology—rated for severity in addition to presence or absence—in at least 3 of 4 sectors for the diagnosis of BPD.83
There are several limitations of the study that should be considered. First, we did not sample probands randomly from a defined source population. Thus, our sampling method may have introduced selection bias if the probands were not representative of individuals in the source population in the 3 groups sampled (ie, individuals with and without BPD, and individuals with MDD). However, the finding that there was no significant interaction between the source of the BPD proband (patient vs community) and measures of the familial aggregation of BPD suggests that the 2 sources of individuals with BPD were similar. We also took care to select individuals without BPD in a manner that did not involve knowledge of whether they had any attributes, such as other forms of psychopathology (except for those that were excluded in all proband groups), that might influence familial aggregation patterns. Because we had very few patient probands with MDD, we were unable to test for such an interaction involving that population. Second, we used weighting based on the inverse probability of selection using a novel estimator of the prevalence of BPD derived from the data on relatives rather than a direct assessment of prevalence. Any additional uncertainty attributable to use of this method is not reflected in the confidence intervals, but any such uncertainty would, in any event, be expected to be small relative to other sources. Furthermore, the weighting method could have introduced bias. However, it is reassuring that the sensitivity analysis showed that the estimates for the familial aggregation of BPD did not change substantially when the analysis was unweighted and was confined to families in the BPD proband group and the non-BPD proband group. Third, to obtain the maximum amount of data from our sample, we used information from families in which the proband was recruited for MDD, but it is possible that either the selection or weighting of this group could have introduced bias. However, the results did not change appreciably when this group was excluded. Fourth, not all eligible parents and siblings chose to participate; the missing data could have introduced bias if the characteristics of the relatives not interviewed were different from those who were interviewed. However, serious bias would be unlikely unless there were a differential effect among proband groups (eg, if ill relatives of BPD probands were more likely to participate than were equally ill relatives of non-BPD probands). Fifth, the lifetime diagnosis of BPD, including its various sectors, is difficult to assess. However, misclassification of this type would be expected to be nondifferential across groups and therefore would likely cause bias toward the null. Sixth, although we found no statistically significant differences in measures of familial aggregation related to sampling source, type of relative, generation, or sex, we had little power to detect such differences; therefore, we may have failed to identify some important differences. Future studies should be large enough to test for these differences, which may have relevance to the causation of the disorder and to treatment approaches. Of additional reassurance is that twin studies have found no evidence of sex effects for BPD,23
for BPD sectors,44
and overall, for cluster B personality disorders.84
In conclusion, BPD and its sectors of psychopathology show substantial familial aggregation, suggesting a causal role for familial factors for the diagnosis of BPD and for each of the sectors. Furthermore, these results, in combination with those from twin studies, suggest that BPD has moderate heritability and that the individual sectors of psychopathology have a somewhat lower level of heritability. Finally, the relationship of BPD to its sectors of psychopathology is best explained by a model whereby the sectors are manifestations of a unitary liability to BPD.