Four limitations need to be noted in interpreting the above results. First, diagnoses were based on fully structured lay interviews with the CIDI. The CIDI typically produces more reliable diagnoses than those based on semi-structured clinical interviews
and their prevalence estimates typically correspond well with those based on clinical reappraisal interviews.
However, fully structured interviews, unlike semi-structured clinical interviews, are unable to clarify symptom responses or check questions across disorders to facilitate differential diagnosis, potentially leading to inflated estimates of comorbidity. As comorbidity is the focus of the current analysis, this is an especially important limitation that should be kept in mind when interpreting results. Second, lifetime diagnoses were based on retrospective reports rather than prospective data, probably leading to recall bias that under-estimated prevalence
and distorted age-of-onset estimates
despite special memory-priming methods used in both surveys.
Third, the models were based on the simplifying assumption that the time-lagged associations among mental disorders are additive. Fourth, the models assumed that there are no differential predictive associations related to age of onset or time since onset of the temporally primary disorders. More in-depth analyses to investigate these assumptions go beyond the scope of this preliminary report.
In the context of these limitations, our finding of a two-factor internalizing-externalizing structure among the DSM-IV disorders is consistent with previous research,[3-5,7-9]
but the NCS-2 and NCS-R results do not support the distinction found in the NCS-A and some other previous studies between distress (e.g., depression, GAD, PTSD) and fear (i.e., panic and phobias) disorders within the internalizing domain. Others also failed to find a distinction between distress and fear disorders.[3,4,17]
This less differentiated structure might be due to our focus on lifetime disorders, whereas 12-month disorders were the focus of most studies that distinguished distress and fear disorders. The fact that the more differentiated picture appears in the NCS-A despite the focus on lifetime disorders might be due to a greater proportion of lifetime disorders are being recent disorders in studies of youth than adults.
Our finding of significant time-lagged associations across virtually all pairs of disorders considered here is broadly consistent with evidence of associations between earlier and later disorders in previous longitudinal studies,[19,22-25,27]
although most previous studies focused on prevalent cases whereas we studied first onsets. We found, again consistent with previous studies, stronger and more consistent time-lagged associations within (homotypic) than between (heterotypic) the internalizing and externalizing domains. However, again like previous studies, we also found significant between-domain time-lagged associations.[25,27]
Our analysis then went beyond previous studies to investigate the role of latent variables in the development of comorbidity. We showed that the vast majority of the 306 pair-wise time-lagged associations among the 18 disorders considered here can be explained by a model that assumes the existence of mediating latent internalizing and externalizing variables. The temporally primary disorders constituting the mediating predictor variables vary substantially in importance in predicting secondary disorders, but the good fit of the model shows that the relative importance of these disorders is quite consistent in predicting a wide range of secondary disorders. This suggests that common pathways are involved in these many predictive associations.
Despite the stability of relative importance of predictor disorders within domains, we also found significant between-domain variation in strength of prediction, with consistently stronger predictive associations within (homotypic) than between (heterotypic) domains. However, temporally primary externalizing disorders were more consistently significant predictors of the subsequent onset of internalizing disorders, with predictive effects nearly as large as those of temporally primary internalizing disorders, than temporally primary internalizing disorders were in predicting subsequent onset of externalizing disorders.
Despite the good fit of the latent variable model, we found a number of significant residual associations between particular pairs of temporally primary and secondary disorders. However, these residual associations were much more common in the NCS-2 and NCS-R data, where the best-fitting model assumed the existence of two latent variables (internalizing, externalizing) than in the NCS-A data, where the best-fitting model assumed the existence of four latent variables (fear, distress, behavior, substance). This raises the possibility that the residual associations represent traces of more differentiated dimensions underlying internalizing and externalizing disorders.
Some of the significant residual associations found in the data are quite intriguing and cannot be accounted for by a simple division of internalizing disorders into separate fear and distress sub-domains or externalizing disorders into behavior and substance domains. For example, a stable negative association was found between temporally primary intermittent explosive disorder (IED) and subsequent drug abuse after controlling for scores on the latent internalizing disorder variable. This negative association could be due to externalizing disorders being made up of multiple dimensions, one or more of which is significantly more strongly related to drug abuse than to IED. Consistent with this possibility, evidence exists that multiple dimensions account for associations among externalizing disorders
and that these underlying dimensions are somewhat different for impulsive aggression (i.e., IED) than substance abuse, with sensation seeking, risk taking, and antisocial personality more strongly related to substance abuse than to impulsive aggression, and global psychopathology more strongly related to impulsive aggression than to substance abuse.[61,62]
A more differentiated latent variable model that includes these externalizing sub-dimensions or a model that includes explicit measures of these predispositions might explain the negative association between IED and subsequent drug abuse in our less differentiated latent variable model.
It is important to caution, though, that these few unique significant residual pair-wise associations should be treated as no more than preliminary due to the problem of multiple testing even though we required a high standard of proof to select them. Replication in other datasets is needed before these associations should be considered reliable. Furthermore, even if they are subsequently found to be reliable, their existence should not deflect attention from our main finding: the consistently significant comorbidities found among the 306 disorder-pairs considered in the three datasets are likely due to common underlying processes that should be the focus of future research on the development of comorbidity. More subtle processes doubtlessly exist, but are likely to become manifest more clearly by controlling the effects of the broadly defined latent variables studied here and searching for consistencies in residual associations that can be fleshed out in more focused studies. Implicitly, our results also caution against interpreting pair-wise associations as unique in focused analyses of particular disorder pairs without first demonstrating, as we did here, that they are specific rather than mere realizations of larger nonspecific processes involving a larger set of internalizing or externalizing disorders.