Class 2 and 3: Positive and Mixed classes

Class 2 had high rates of positive symptoms and class 3 (comprising nearly a third of the cases) was a mixed symptom group. The positive symptoms contained in Class 2 and 3 include the following items: auditory hallucinations, global hallucination score, global delusion score and commenting voices. The presence of positive symptoms is considered an integral part of the understanding of schizophrenia. These two groups thus intuitively fit within our understanding of schizophrenia. Indeed, hallucinations, especially auditory and visual types are experienced by more than 70% of individuals with schizophrenia during the course of their illness (Baethge et al.

2005) and one study reported 70% of patients experienced auditory and visual hallucinations simultaneously (Gauntlett-Gilbert and Kuipers 2003).

Indeed, changes have occurred in our understanding of the importance of specific delusions in the diagnosis of schizophrenia. Schneiderian first-rank symptoms such as delusions of control,

thought insertion, withdrawal and broadcasting were traditionally viewed as more important delusions. However, we now know that persecutory and reference delusions actually occur more commonly in schizophrenia (Mellor 1970, Tandon et al. 2009). The same issue arose in

hallucinations where the classical Schneiderian first-rank hallucinations namely conversing and commenting voices actually occurs less frequently in schizophrenia than threatening or accusatory voices (Tandon et al. 2009). This finding is mirrored in our study with the most common delusions being life-time paranoid delusions (88.5%) and delusions of reference (53.5%).

Despite the high prevalence of hallucinations and delusions there appear to be a caveat in terms of the several aspects of these symptoms including „What is the real life prevalence rate of these symptoms” and what is the course of fluctuations and the temporal relationships to these

fluctuations? (Oorschot 2012). Maher et al. (1974) argued that delusions stem from the attempts to interpret the anomalous hallucinatory experiences and this early theory seems to be supported

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by the strong association between the presence of hallucinations and delusions (Liddle and Barnes 1990, van Os et al. 2000) as well as the increased risk for psychosis if hallucinations are followed by delusional interpretation (Krabbendam and van Os 2005). However, the reverse mechanism might also be possible with delusions affecting the inner experiences and source-monitoring mechanism (Kapur 2003, van 't Wout et al. 2004).

Attempts in subtyping schizophrenia on the basis of symptomatology showed some heterogeneity with paranoid and Schneiderian delusions loading on separate factors in two studies (Liddle 1987, de Leon et al. 1993). Despite these earlier studies subsequent attempts mostly used subscale level scores and thus assumed that all items within the subscale contributed equally to the factor

solution (Andreasen et al. 1995). Peralta and Cuesta (1998) questioned the wisdom of such an approach and showed that in their sample the best fit was for a more complex five factor model (albeit the fit not perfect). Their finding supported the earlier data in that Schneiderian delusions had the best variance value, while non-Schneiderian delusions seemed very heterogeneous in nature. Nevertheless hallucinations and delusions did still covary. If a two factor model was fitted, the psychosis factor (hallucinations and delusions) was associated with a later age of onset, while the disorganized factor was associated with a lower age at onset and increased illness

severity. These finding support the need for an item level approach as per our study as subscale or total score approaches might obscure important findings for subtyping.

The DSM-V supports a dimensional approach to the diagnosis of schizophrenia and in essence class 2 and 3 might merely be representative of degrees of severity within the spectrum (APA 2013, Heckers et al. 2013). Our study does not include a detailed cognitive assessment or a qualitative assessment of mood or anxiety symptoms. When this study was designed the categorical approach to schizophrenia symptoms was followed. This turned out to be a major drawback as it makes it very difficult to ascertain whether class 2 and 3 might differ in terms of

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these other domains (i.e. mood or cognitive impairment) and not merely differs in terms of the severity of psychotic symptoms. The meta-analysis of 104 studies investigating the relationship between neurocognition and disorganization performed by Ventura et al. (2010) may shed some light on this. Ventura et al. (2010) reports a weak relationship between reality distortion and neurocognition (r=−.04; p=.03) overall and in all six of the individual neurcognitive domains.

Although these findings do not exclude interactions between reality distortion and neurocognition, they do support a dimensional view of positive symptoms distinguishing disorganization from reality distortion.

It can however be argued that positive symptoms vary to such a degree across the lifespan of a patient, that is almost impossible to use this a method for subtyping schizophrenia. Indeed, Schultz et al. (1996) already looked at this issue. They studied a group of 391 patients (ages 14 through 73) with schizophrenia, schizo-affective disorder and schizophrenifrom disorder in terms of psychotic, disorganised and negative symptoms. They found the effect of age to be significant in a negative direction for positive and disorganized symptoms, but no effect for formal thought disorder or negative symptoms.

Of specific interest is whether family history has any relationship with these positive symptoms.

A review by Esterberg et al. (2010) shed some light on this. Using studies that reported on family history and age-at-onset (N=15 studies), age-at-onset and sex (N=12 studies), and/or positive (N=11 studies) and negative symptoms (N=12 studies) they demonstrated a small but significant impact on age-at-onset and negative symptoms, but not positive symptoms. Indeed, patients with a family history of schizophrenia had more negative symptoms. However, one should consider earlier individual studies i.e. McGuffin et al. (1991) and Basset et al. (1993) that suggests a liability/threshold model in which positive and mixed positive/negative forms of schizophrenia differed quantitatively along the same continuum of liability. McGuffin et al. (1991) goes further

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to suggest that the positive symptom form may be less severe than the mixed form. Addington and Addington (1991), using the SAPS and SANS in 41 schizophrenia subjects in the acute phase and six months later, found no inverse relationship between positive and negative symptoms and the phase of illness. Again negative symptoms seem more constant across acute and follow-up period. This finding is interesting as our data showed a relatively large group with mixed positive and negative symptoms. In terms of subtyping the mixed group might be the more stable group in terms of symptom profile, but it is intriguing that the positive symptom group (group 2) exist as a separate entity. Future projects should include a longitudinal assessment of this group to see whether they remain truly positive or whether they revert to a low or no symptom group as the disease progress or at different time points within the illness course.