This study extended research on the quantitative reorganization of psychiatric nosology in several ways. First, it confirmed the basic internalizing-externalizing framework in a severely ill cohort. These spectra appear to be robust across ages and cultures, and we now observed them in an inpatient sample. Second, we sought to incorporate schizophrenia and schizotypal personality disorder in the quantitative framework and found that these conditions do not belong to the internalizing or externalizing domains but define a separate spectrum. Third, we examined the validity of the resulting cluster with regard to family history and long-term course. The schizophrenic spectrum was coherent and clearly distinct from the internalizing and externalizing conditions on both validators. Our results agree well with prior research that argued for a separate schizophrenic cluster25–27
and provide some of the first direct evidence in support of this proposal. They also confirm the decision of framers of ICD-10 to place schizotypal disorder with schizophrenia rather than with personality disorders.
Our findings need to be considered against the limitations of the present investigation. Although broader than many prior studies, our analysis was still limited to only 11 syndromes. Future investigations need to include many more conditions to explicate a comprehensive quantitative classification. Another limitation is that only a partial assessment of anxiety disorders was possible, which prevented us from testing distinctions within the internalizing cluster (ie, fear and distress subclusters). Also, the syndromes were based on DSM-III-R rather than on DSM-IV criteria. Fortunately, the majority of syndromes considered were identical in the 2 manuals, and others showed only minor differences. In addition, schizotypal personality was assessed after onset of psychosis. Although personality ratings were made by experienced interviewers under explicit instructions of capturing long-standing characteristics and were based on information from multiple sources collected soon after first admission, the assessment may have been affected by behavioral changes that occurred since illness onset. Furthermore, long-term course and family history ratings were made by interviewers who were not blind to diagnoses. Validity data were usually collected many years after the 6-month wave, and syndromes used in this study are not full DSM diagnoses that were accessible to interviewers, but some confounding may have occurred nevertheless. Furthermore, the present study was focused on a specific population (individuals with a history of hospitalization for psychosis), and a replication in a less selective patient sample is necessary. On balance, the nature of this cohort is a strength because employment of this epidemiological first-admission sample gave us a rare opportunity to study the diagnostic picture that was free from distortions associated with chronic illness and long history of medication use. Moreover, the patients were drawn from a broad range of inpatient facilities that covered an entire county, thus reducing selection biases. Furthermore, this cohort was followed for 10 years with multiple interim assessments, which allowed us to examine the predictive validity of the proposed clusters.
Despite the limitations noted above, the present study provided important new information on the placement of schizophrenia and schizotypal personality disorder in the quantitative framework. This knowledge can be valuable because the emerging classification promises to improve our understanding of psychopathology in several respects. First, factor analytically derived spectra appear to be directly tied to common genetic liabilities and can facilitate etiologic research. Twin studies indicated that the internalizing and externalizing spectra capture much of the genetic vulnerability to common mental disorders.17–19
Similarly, there is evidence for a distinct and coherent genetic factor underlying the schizophrenic cluster.49,50
In fact, molecular genetic studies are beginning to uncover specific genes contributing to the 2 established spectra,51–53
and we hope that our findings will stimulate parallel research on the schizophrenic spectrum.
Second, the clusters may reflect certain fundamental neurobiological abnormalities. For instance, the internalizing spectrum appears to be linked to amygdala hyperactivity because it has been implicated in both anxiety and depression.54–56
The externalizing domain may be associated with functioning of ventromedial prefrontal cortex, which seems to be involved both in substance abuse and in antisocial behavior.57–59
The schizophrenic cluster may be linked with gray matter volume deficits, especially in the temporal lobe and thalamus because these abnormalities have been observed both in schizophrenia and in schizotypal personality disorders.28,29
Delineation of this cluster’s boundaries may lead to more powerful designs for investigating pathophysiology of psychosis.29
Third, the quantitative organization may explain and predict efficacy of psychotropic medications. For example, selective serotonin reuptake inhibitors had been regarded as antidepressants but were found to be efficacious in treating anxiety disorders as well.60
In contrast, their efficacy has not been established in schizophrenia.27,60
These observations are consistent with the distinction between internalizing and schizophrenic spectra, which supports the contention that the quantitative organization can inform intervention research. Finally, the proposed arrangement arguably increases the coherence of the classification system and facilitates differential diagnosis by grouping disorders on the basis of empirical association rather than surface similarity.
It is important to acknowledge that the present study evaluated only 2 candidates for membership in the schizophrenic cluster. A number of other candidates have been suggested by factor analytic investigations of psychiatric symptoms. In the most comprehensive study of this kind, Markon61
analyzed various Axis I and II symptoms and found a spectrum defined by features of schizotypal, schizoid, paranoid, and obsessive-compulsive personality disorders as well as frank psychosis. Markon's results largely agree with factor analytic studies of Axis II conditions. A quantitative review of this literature concluded that schizotypal, schizoid, and paranoid personality disorders cluster together, although obsessive-compulsive personality disorder belongs to a different spectrum.62
Other research identified strong links between schizotypal personality and dissociation.63,64
There is also evidence that obsessive-compulsive disorder and bipolar disorder are related to schizophrenic disorders, but the supporting evidence is rather mixed.27,61,63
In the present study, obsessive-compulsive disorder fell in the internalizing rather than the schizophrenic cluster, which is consistent with prior factor analytic investigations.61,65
We did not evaluate bipolar disorder, but recent literature reviews concluded that support for its inclusion in the schizophrenic spectrum is insufficient.27
In sum, the leading candidates for addition to the schizophrenic cluster are dissociative disorders as well as schizoid and paranoid personality disorders, and they need to be evaluated in future studies.
Several other observations warrant comment. Importantly, the DSM-IV organization failed to represent the data adequately, despite being the most elaborate of the models considered. Indeed, quantitative organizations were clearly superior to it. It also was apparent that the existing nosology cannot account for pronounced similarities between schizophrenia and schizotypal syndromes with regard to family history and illness course. Although these conditions are allocated to different axes presently, we found that they were much more similar to each other than either was to other Axis I and Axis II variables considered. This observation is consistent with prior research on familial aggregation of schizophrenia and schizotypal personality disorder25,27
and extends it by validating the schizophrenic cluster directly. Also, our study provided novel evidence for the validity of this cluster with regard to long-term illness course. Finally, we should note that when the hierarchical exclusion for mood disturbance was relaxed, the correlation between schizophrenia syndrome and major depression was essentially zero (), which indicates that patients with schizophrenia syndrome were no less likely to experience lifetime depression than participants with other severe illnesses. Thus, our data suggest that concomitant depression should not be an exclusion for a schizophrenia diagnosis. This conclusion is consistent with prior research, which argued that these 2 conditions are not mutually exclusive.66–68
In conclusion, our study provided early direct evidence for a separate schizophrenic cluster. It also confirmed the internalizing and externalizing spectra in a new population. These findings underscore the need to reorganize the diagnostic system, especially because the DSM model fit the data very poorly and was not aligned with patterns of family history and long-term course. Specifically, our findings and results of prior research imply that unipolar depression and some anxiety disorders should be placed together in the internalizing cluster.10,69
Schizotypal and antisocial personality disorders may be better placed on Axis I with schizophrenia and substance use disorders, respectively. In fact, among other proposals, the DSM-V Personality Disorders Work Group is considering relocation of personality disorders to Axis I.70
It also appears that conduct disorder would fit well with antisocial personality and substance use disorders. Of note, ICD-10 already places schizophrenia and schizotypal disorder together, but it still splits internalizing conditions and externalizing conditions across different rubrics. Beyond these initial recommendations, the outline of the quantitative classification remains rough, but it is almost certain that development of nosology that captures natural patterns of mental illness will greatly enhance the validity and practical utility of psychiatric diagnosis. The present study brings us 1 step closer to a truly empirical classification of mental illness.