Clinical relevance of general and specific dimensions in bifactor models of psychotic disorders
Authors: Victor Peralta, Gustavo J. Gil‐Berrozpe, Ana Sánchez‐Torres, Manuel J. Cuesta
Journal: World Psychiatry (2021)

Increasing empirical evidence indicates that psychotic disorders are more accurately understood as continuously distributed dimensions of psychopathology, which can be arranged in a hierarchical structure framework1. Bifactor models are a subset of hierarchical models that can inform several important questions about the structure and external validity of psychopathology, including the nature of the general factor given the pattern of symptom loadings, the amount of variance in the specific factors due to the general factor, and the unique external correlates of the general and specific factors2, 3. While previous studies of bifactor models in psychotic disorders outlined the clinical and research relevance of separating general and specific psychopathology4, 5, most of them have been limited by one or more problems regarding sample size, sample representativeness, symptomatic coverage and systematic external validation. Of particular concern are the conflicting results in the literature regarding the nature and validity indicators of the general psychosis factor. Using a broad sample of subjects with the full spectrum of psychotic disorders, we tested the construct validity of alternative bifactor models of symptoms, and the criterion validity of the factors in the best-fitting model against 21 external validators, including antecedents, illness-related features, treatment-related variables and psychosocial impairment. The study population consisted of 2,240 subjects with a diagnosis of a DSM-IV functional psychotic disorder from a defined catchment area in Navarra (Spain)6, and included three subsamples: first-episode admissions (N=486), multi-episode admissions (N=660) and outpatients (N=1,094). In the whole study sample, 57% of subjects were male, the mean age was 38.7±15.2 years, and the mean Global Assessment of Functioning scale score was 65.4±20.8. DSM-IV diagnoses included schizophrenia (N=908), schizophreniform disorder (N=180), delusional disorder (N=120), brief psychotic disorder (N=179), schizoaffective disorder (N=124), bipolar disorder (N=345), major depressive disorder (N=245) and psychotic disorders not otherwise specified (N=139). Subjects underwent an extensive clinical examination by the Comprehensive Assessment of Symptoms and History (CASH). Bifactor models were estimated in each subsample and in the total sample to establish the best-fitting model using the omegaSem routine in the R package. Seven alternative models were estimated using multiple information criteria, including X2, log-likelihood, Akaike information criterion (AIC), Bayesian information criterion (BIC), sample-size adjusted Bayesian information criterion (SABIC), confirmatory fit index, Tucker-Lewis index and root mean square error of approximation. Following identification of the best-fitting model, we examined its validity against the external indicators using linear regression. As an omnibus test of the associations between each factor and the validators, we used the general linear model, with partial ɳ2 indicating the percentage of the unique variance in each of the factors that is explained by the validators. To avoid false positive findings, p was set at <0.01. For all fit measures compared, the best-fitting model in each subsample and in the whole sample was a model comprising a general factor and six specific factors of diminished expressivity, avolition-anhedonia, reality distortion, disorganization, mania and depression. The difference in AIC, BIC and SABIC parameters between this model and that with the second better fit was >211 in each subsample and in the whole sample, indicating very strong support for the superiority of this model over the others. Factor loadings on the general factor were relatively large for disorganization symptoms (mean λ=.58), moderate for negative symptoms (mean λ=.44), low for reality distortion symptoms (mean λ=.23) and very low for mood symptoms (mean λ=.16). The amount of variance in the symptom scores that was accounted for by the general and specific factors was 61% and 31%, respectively. The general factor exhibited more significant associations with the validators than any other factor, since it predicted most of the validators and explained 54% of their variance. The general factor score was significantly related to familial risk of schizophrenia (β=.056, 95% CI: .020-.125), poor educational performance (β=.165, 95% CI: .125-.205), childhood adversity (β=.065, 95% CI: .024-.105), poor premorbid adjustment (β=.155, 95% CI: .118-.191), duration of untreated psychosis (β=.110, 95% CI: .072-.174), early age at illness onset (β=.194, 95% CI: .153-.234), chronic illness onset (β=.140, 95% CI: .102-.179), number of hospitalizations (β=.107, 95% CI: .067-.148), cognitive impairment (β=.286, 95% CI: .249-.322), chronic illness course (β=.129, 95% CI: .092-.176), dose-years of antipsychotics (β=.060, 95% CI: .019-.100), current dose of antipsychotics (β=.596, 95% CI: .562-.622), poor treatment response (β=.176, 95% CI: .138-.213), and four domains of psychosocial functioning impairment (β=.223, 95% CI: .138-.290). In decreasing order of importance, the contribution of the individual specific factors in explaining the validity indicators was as follows: avolition-anhedonia 36%, diminished expressivity 26%, depression 23%, reality distortion 18%, mania 12%, and disorganization 8%. The strongest association of both diminished expressivity and avolition-anhedonia factors was with social impairment (β=.212, 95% CI: .168-.252, and β=.436, 95% CI: .402-.488, respectively). The strongest association of reality distortion, disorganization, mania and depression factors was with current dose of antipsychotics (β=.364, 95% CI: .336-.394), poor response to treatment (β=.136, 95% CI: .099-.173), familial risk of bipolar disorder (β=.227, 95% CI: .182-.251) and polypharmacy (β=.438, 95% CI: .397-.478), respectively. In summary, the construct validity of the bifactor model with six specific factors was verified by statistical fit indices. The psychosis general factor accounted for a majority of the variance among symptoms and was the factor most often related to external indicators, explaining 54% of their variation, all of which posits the general factor as a core construct of psychotic pathology. The observed association pattern of the general factor with external validators suggests that it may be indexing both a neurodevelopmental signature of psychotic disorders and a marker of overall illness severity. Furthermore, these findings are broadly consistent with the hypothesis that the general psychosis factor might be at the extreme end of severity of the general psychopathology factor8. Despite not being an explicit component of psychiatric nosology, the general psychosis factor provides an organizing model for understanding psychotic disorders that might have important implications for predicting relevant risk factors and clinical features9. Although a direct causal interpretation is not possible, the external correlates of the general psychosis factor might be meaningful for clinical practice. Assessing for the general factor could allow the identification of relevant background variables and clinical features in subjects with psychotic disorders, who may benefit from careful clinical monitoring and possibly more tailored interventions. For instance, a high score on the general factor, irrespective of diagnostic categories, may alert the clinician about the risk of a broad range of poor clinical outcomes.